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The skin-penetrating gastrointestinal parasitic nematode Strongyloides stercoralis causes strongyloidiasis, which is a neglected tropical disease that is associated with severe chronic illness and fatalities. Unlike other human-infective nematodes, S. stercoralis cycles through a single free-living generation and thus serves as a genetically tractable model organism for understanding the mechanisms that enable parasitism. Techniques such as CRISPR/Cas9-mediated mutagenesis and transgenesis are now routinely performed in S. stercoralis by introducing exogenous DNA into free-living adults and then screening their F1 progeny for transgenic or mutant larvae. However, transgenesis in S. stercoralis has been severely hindered by the inability to establish stable transgenic lines that can be propagated for multiple generations through a host; to date, studies of transgenic S. stercoralis have been limited to heterogeneous populations of transgenic F1 larvae. Here, we develop an efficient pipeline for the generation of stable transgenic lines in S. stercoralis. We also show that this approach can be used to efficiently generate stable transgenic lines in the rat-infective nematode Strongyloides ratti. The ability to generate stable transgenic lines circumvents the limitations of working with heterogeneous F1 populations, such as variable transgene expression and the inability to generate transgenics of all life stages. Our transgenesis approach will enable novel lines of inquiry into parasite biology, such as transgene-based comparisons between free-living and parasitic generations.

Strongyloides stercoralis, commonly known as the human threadworm, is a skin-penetrating gastrointestinal parasitic nematode that infects hundreds of millions of people worldwide. Like other Strongyloides species, S. stercoralis is capable of cycling through a single free-living generation. Although S. stercoralis and the free-living nematode Caenorhabditis elegans are evolutionarily distant, the free-living adults of S. stercoralis are similar enough in size and morphology to C. elegans adults that techniques for generating transgenics and knockouts in C. elegans have been successfully adapted for use in S. stercoralis. High-quality genomic and transcriptomic data are also available for S. stercoralis. Thus, one can use a burgeoning array of functional genomic tools in S. stercoralis to probe questions about parasitic nematode development, physiology, and behavior. Knowledge gained from S. stercoralis will inform studies of other parasitic nematodes such as hookworms that are not yet amenable to genetic manipulation. This review describes the basic anatomy of S. stercoralis.

Hookworms are soil-transmitted parasitic nematodes that penetrate the host skin before migrating to the lungs. With an estimated 500-700 million people infected worldwide, hookworm infections are a neglected tropical disease and a significant cause of morbidity, particularly in children, pregnant women, and immunocompromised individuals. Although there is ample evidence that complement activation is pivotal to elicit a protective host immune response against invasive pathogens, its role in hookworm infection remains insufficiently explored. Here, we investigated the complement anaphylatoxin, C5a, during the early lung stage of infection with Nippostrongylus brasiliensis in C57BL/6J wild type and C5aR1-/- mice. Despite the previously reported ability of lung larvae to evade complement activation, C5a was detectable locally in lung tissue and bronchoalveolar lavages. Surprisingly, C5aR1 presence directly contributed to the pathogenicity of hookworm infection. The burden of viable parasites in the lungs was mitigated in C5aR1-/- mice, compared to C57BL/6J mice 48 hours post-infection. Additionally, C5aR1-/- mice showed significantly reduced lung injury, lower cytokine release, attenuated alveolar hemorrhage, and limited alveolar-capillary barrier disruption. Neutrophils were the most abundant and highest C5aR1-expressing cell type in the alveolar space after infection. Deficiency of C5aR1 reduced the influx of neutrophils, monocytes, and eosinophils to the pulmonary airways. RNA sequencing of alveolar neutrophils revealed C5aR1-dependent regulation of the novel nuclear protein, DEDD2. In conclusion, our findings highlight the impact of C5aR1 signaling in neutrophils during hookworm infection uncovering an unexpected downside of complement activation in parasitic infection. [ABSTRACT FROM AUTHOR]

Hookworms are soil-transmitted parasitic nematodes that penetrate the host skin before migrating to the lungs. With an estimated 500-700 million people infected worldwide, hookworm infections are a neglected tropical disease and a significant cause of morbidity, particularly in children, pregnant women, and immunocompromised individuals. Although there is ample evidence that complement activation is pivotal to elicit a protective host immune response against invasive pathogens, its role in hookworm infection remains insufficiently explored. Here, we investigated the complement anaphylatoxin, C5a, during the early lung stage of infection with Nippostrongylus brasiliensis in C57BL/6J wild type and C5aR1-/- mice. Despite the previously reported ability of lung larvae to evade complement activation, C5a was detectable locally in lung tissue and bronchoalveolar lavages. Surprisingly, C5aR1 presence directly contributed to the pathogenicity of hookworm infection. The burden of viable parasites in the lungs was mitigated in C5aR1-/- mice, compared to C57BL/6J mice 48 hours post-infection. Additionally, C5aR1-/- mice showed significantly reduced lung injury, lower cytokine release, attenuated alveolar hemorrhage, and limited alveolar-capillary barrier disruption. Neutrophils were the most abundant and highest C5aR1-expressing cell type in the alveolar space after infection. Deficiency of C5aR1 reduced the influx of neutrophils, monocytes, and eosinophils to the pulmonary airways. RNA sequencing of alveolar neutrophils revealed C5aR1-dependent regulation of the novel nuclear protein, DEDD2. In conclusion, our findings highlight the impact of C5aR1 signaling in neutrophils during hookworm infection uncovering an unexpected downside of complement activation in parasitic infection.

Soil-transmitted parasitic nematodes infect over one billion people and cause devastating morbidity worldwide. Many of these parasites have infective larvae that locate hosts using thermal cues. Here, we identify the thermosensory neurons of the human threadworm Strongyloides stercoralis and show that they display unique functional adaptations that enable the precise encoding of temperatures up to human body temperature. We demonstrate that experience-dependent thermal plasticity regulates the dynamic range of these neurons while preserving their ability to encode host-relevant temperatures. We describe a novel behavior in which infective larvae spontaneously reverse attraction to heat sources at sub-body temperatures and show that this behavior is mediated by rapid adaptation of the thermosensory neurons. Finally, we identify thermoreceptors that confer parasite-specific sensitivity to body heat. Our results pinpoint the parasite-specific neural adaptations that enable parasitic nematodes to target humans and provide the foundation for drug development to prevent human infection.

Goats and sheep are small ruminants that are widely used as livestock by the people of Indonesia. One of them is in Petir Village, Dramaga Sub-District, Bogor District. Increasing livestock productivity can be achieved by paying attention to aspects of livestock health. Ruminants often get infection by parasitic worms. Treatment of parasitic helminth infections can be carried out by the administration of anthelmintic and supportive treatment with vitamins administration. This activity aims to improve the health of small ruminants by administering anthelmintic to deworming and vitamins to support livestock productivity. This activity begins with the examination of fecal samples from livestock to diagnose parasitic helminth infections. The results of the examination are used as a basis for carrying out treatment in the form of administering deworming and vitamins. The results of the examination of fecal samples were obtained as many as 66.67% found of positive helminth infection and 46.67% positive of oocysts. Common clinical symptoms are found like have diarrhea and have thin bodies. Treatment has been carried in nine farms of sheep and goat in the village. This activity received support from residents, especially sheep and goat farmers. The anthelmintic and vitamin administration to small ruminants has been carried out well and is part of efforts to increase livestock productivity in Bogor District.

Gastropod-nematode associations are underreported worldwide. In the present study, juvenile and adult nematodes were found in the freshwater gastropod Burnupia stenochorias (Melvill & Ponsonby, 1903), from the Vaal River, South Africa. The nematodes were confirmed to belong to the genus Daubaylia chitwood & chitwood, 1934 (Daubayliidae). This is the first report of Daubaylia from a snail belonging to the family Burnupiidae, and the first report of this nematode taxon in southern Africa. Like D. pearsoni and D. malayanum from Australia and Malaysia respectively, adult females of the current species possess multiple well-developed eggs in the uteri, with larvae developing in utero. Morphological and molecular characteristics showed that the nematodes are distinct from all the described species of Daubaylia. Thus, they are considered a new species, Daubaylia burnupiae n. sp. The species differs from its congeners based on spicule shape, the short tail of the male, an anal cuticular knob-like protrusion on the female, and oesophagi with short isthmi and short glandular basal bulbs in both sexes. Three club-shaped pharyngeal lobes, extending slightly above the surface of the cephalic lips in both sexes and a pre-cloacal median papilla on the male were described using scanning electron microscopy, the first of such observations for the daubayliids. Genetic analyses showed that partial sequences of D. burnupiae n. sp. differed from species for which genetic data are available, by at least 26 and 9 base pair differences for 28S and 18S rDNA, respectively. Our results show that low prevalence and abundance of nematodes in the snails, corresponded with increased pollution in the river. We suspect that exposure to pollutants reduces the viability of the infective gravid female nematode during transmission. Therefore, the nematode is a potential bioindicator for aquatic pollution.

Approximately 800 million people worldwide are infected with one or more species of skin-penetrating nematodes. These parasites persist in the environment as developmentally arrested third-stage infective larvae (iL3s) that navigate toward host-emitted cues, contact host skin, and penetrate the skin. iL3s then reinitiate development inside the host in response to sensory cues, a process called activation. Here, we investigate how chemosensation drives host seeking and activation in skin-penetrating nematodes. We show that the olfactory preferences of iL3s are categorically different from those of free-living adults, which may restrict host seeking to iL3s. The human-parasitic threadworm Strongyloides stercoralis and hookworm Ancylostoma ceylanicum have highly dissimilar olfactory preferences, suggesting that these two species may use distinct strategies to target humans. CRISPR/Cas9-mediated mutagenesis of the S. stercoralis tax-4 gene abolishes iL3 attraction to a host-emitted odorant and prevents activation. Our results suggest an important role for chemosensation in iL3 host seeking and infectivity and provide insight into the molecular mechanisms that underlie these processes.

Gastropod-nematode associations are underreported worldwide. In the present study, juvenile and adult nematodes were found in the freshwater gastropod Burnupia stenochorias (Melvill & Ponsonby, 1903), from the Vaal River, South Africa. The nematodes were confirmed to belong to the genus Daubaylia chitwood & chitwood, 1934 (Daubayliidae). This is the first report of Daubaylia from a snail belonging to the family Burnupiidae, and the first report of this nematode taxon in southern Africa. Like D. pearsoni and D. malayanum from Australia and Malaysia respectively, adult females of the current species possess multiple well-developed eggs in the uteri, with larvae developing in utero. Morphological and molecular characteristics showed that the nematodes are distinct from all the described species of Daubaylia. Thus, they are considered a new species, Daubaylia burnupiae n. sp. The species differs from its congeners based on spicule shape, the short tail of the male, an anal cuticular knob-like protrusion on the female, and oesophagi with short isthmi and short glandular basal bulbs in both sexes. Three club-shaped pharyngeal lobes, extending slightly above the surface of the cephalic lips in both sexes and a pre-cloacal median papilla on the male were described using scanning electron microscopy, the first of such observations for the daubayliids. Genetic analyses showed that partial sequences of D. burnupiae n. sp. differed from species for which genetic data are available, by at least 26 and 9 base pair differences for 28S and 18S rDNA, respectively. Our results show that low prevalence and abundance of nematodes in the snails, corresponded with increased pollution in the river. We suspect that exposure to pollutants reduces the viability of the infective gravid female nematode during transmission. Therefore, the nematode is a potential bioindicator for aquatic pollution. [Display omitted] • Description of a parasitic nematode Daubaylia burnupiae n. sp. from snail Burnupia stenochorias. • This is only the second species of Daubaylia reported in Africa. • Additional features of the family Daubayliidae are highlighted by scanning electron microscopy. • Inclusion of Daubaylia bonaerensis Camino and Gonzalez (2011) in the genus is questionable. • Reduced nematode prevalence and abundance corresponded with increased pollution. [ABSTRACT FROM AUTHOR]

Infection with gastrointestinal parasitic nematodes is a major cause of chronic morbidity and economic burden around the world, particularly in low-resource settings. Some parasitic nematode species, including the human-parasitic threadworm Strongyloides stercoralis and human-parasitic hookworms in the genera Ancylostoma and Necator, feature a soil-dwelling infective larval stage that seeks out hosts for infection using a variety of host-emitted sensory cues. Here, we review our current understanding of the behavioral responses of soil-dwelling infective larvae to host-emitted sensory cues, and the molecular and cellular mechanisms that mediate these responses. We also discuss the development of methods for transgenesis and CRISPR/Cas9-mediated targeted mutagenesis in Strongyloides stercoralis and the closely related rat parasite Strongyloides ratti. These methods have established S. stercoralis and S. ratti as genetic model systems for gastrointestinal parasitic nematodes and are enabling more detailed investigations into the neural mechanisms that underlie the sensory-driven behaviors of this medically and economically important class of parasites.

Parasitic helminth infections are the most common source of neglected tropical disease among impoverished global communities. Many helminths infect their hosts via an active, sensory-driven process in which environmentally motile infective larvae position themselves near potential hosts. For these helminths, host seeking and host invasion can be divided into several discrete behaviors that are regulated by both host-emitted and environmental sensory cues, including heat. Thermosensation is a critical sensory modality for helminths that infect warm-blooded hosts, driving multiple behaviors necessary for host seeking and host invasion. Furthermore, thermosensory cues influence the host-seeking behaviors of both helminths that parasitize endothermic hosts and helminths that parasitize insect hosts. Here, we discuss the role of thermosensation in guiding the host-seeking and host-infection behaviors of a diverse group of helminths, including mammalian-parasitic nematodes, entomopathogenic nematodes, and schistosomes. We also discuss the neural circuitry and molecular pathways that underlie thermosensory responses in these species.

The skin-penetrating gastrointestinal parasitic nematode Strongyloides stercoralis causes strongyloidiasis, which is a neglected tropical disease that is associated with severe chronic illness and fatalities. Unlike other human-infective nematodes, S. stercoralis cycles through a single free-living generation and thus serves as a genetically tractable model organism for understanding the mechanisms that enable parasitism. Techniques such as CRISPR/Cas9-mediated mutagenesis and transgenesis are now routinely performed in S. stercoralis by introducing exogenous DNA into free-living adults and then screening their F1 progeny for transgenic or mutant larvae. However, transgenesis in S. stercoralis has been severely hindered by the inability to establish stable transgenic lines that can be propagated for multiple generations through a host; to date, studies of transgenic S. stercoralis have been limited to heterogeneous populations of transgenic F1 larvae. Here, we develop an efficient pipeline for the generation of stable transgenic lines in S. stercoralis. We also show that this approach can be used to efficiently generate stable transgenic lines in the rat-infective nematode Strongyloides ratti. The ability to generate stable transgenic lines circumvents the limitations of working with heterogeneous F1 populations, such as variable transgene expression and the inability to generate transgenics of all life stages. Our transgenesis approach will enable novel lines of inquiry into parasite biology, such as transgene-based comparisons between free-living and parasitic generations., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9‐targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9‐mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration. [ABSTRACT FROM AUTHOR]

Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia, they use ubiquinone (UQ), but in anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change of substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019); however, the mechanism of substrate selection is not known. Here, we show helminths synthesize two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that synthesize RQ. We show that in Caenorhabditis elegans COQ-2e is required for efficient RQ synthesis and survival in cyanide. Importantly, parasites switch from COQ-2a to COQ-2e as they transit into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.

Parasitic helminths infect over a billion humans. To survive in the low oxygen environment of their hosts, these parasites use unusual anaerobic metabolism — this requires rhodoquinone (RQ), an electron carrier that is made by very few animal species. Crucially RQ is not made or used by any parasitic hosts and RQ synthesis is thus an ideal target for anthelmintics. However, little is known about how RQ is made and no drugs are known to block RQ synthesis. C. elegans makes RQ and can use RQ-dependent metabolic pathways — here, we use C. elegans genetics to show that tryptophan degradation via the kynurenine pathway is required to generate the key amine-containing precursors for RQ synthesis. We show that C. elegans requires RQ for survival in hypoxic conditions and, finally, we establish a high throughput assay for drugs that block RQ-dependent metabolism. This may drive the development of a new class of anthelmintic drugs. This study is a key first step in understanding how RQ is made in parasitic helminths.

Sheep play an important role in national economy and social economy in rural areas in Iran. The main goal of this study was to investigate the fauna and frequency of parasitic helminth infections prevalent in native sheep in Hamedan, western Iran. From April 2010 to March 2011, the gastrointestinal and respiratory tracts of 100-sheep were examined using conventional parasitological methods. The overall infection rate was found as 69%. No infection was found in esophagus and rumens. Parabronema skerjabini (22%) and Ostertagia circumcincta (1%) were recorded as the maximum and minimum cases for the presence of nematode, respectively. On the other hand, the most dominant of trematode and cestode were Fasciola hepatica (13%) and Monezia expansa (13%), respectively. The highest infection rate was reported in summer (84%). The prevalence of helminth infection was varied among gender, seasons and age groups. In conclusion, this is the first report of parasitic helminth infections in sheep in Hamedan province in western Iran. Our results provide baseline information for the future studies.

Graphical abstract Highlights • Thermosensation is a critical sensory modality for many parasitic helminth species. • Thermal cues drive multiple behaviors necessary for host seeking and host invasion. • The neural and molecular basis of parasite thermosensation is understudied. • Parasite thermosensation requires sensory cascades found in free-living nematodes. Abstract Parasitic helminth infections are the most common source of neglected tropical disease among impoverished global communities. Many helminths infect their hosts via an active, sensory-driven process in which environmentally motile infective larvae position themselves near potential hosts. For these helminths, host seeking and host invasion can be divided into several discrete behaviors that are regulated by both host-emitted and environmental sensory cues, including heat. Thermosensation is a critical sensory modality for helminths that infect warm-blooded hosts, driving multiple behaviors necessary for host seeking and host invasion. Furthermore, thermosensory cues influence the host-seeking behaviors of both helminths that parasitize endothermic hosts and helminths that parasitize insect hosts. Here, we discuss the role of thermosensation in guiding the host-seeking and host-infection behaviors of a diverse group of helminths, including mammalian-parasitic nematodes, entomopathogenic nematodes, and schistosomes. We also discuss the neural circuitry and molecular pathways that underlie thermosensory responses in these species. [ABSTRACT FROM AUTHOR]

Eukaryotic forms of life have been continually invaded by microbes and larger multicellular parasites, such as helminths. Over a billion years ago bacterial endosymbionts permanently colonized eukaryotic cells leading to recognized organelles with a distinct genetic lineage, such as mitochondria and chloroplasts. Colonization of our skin and mucosal surfaces with bacterial commensals is now known to be important for host health. However, the contribution of chronic virus and parasitic infections to immune homeostasis is being increasingly questioned. Persistent infection does not necessarily equate to exhibiting a chronic illness: healthy hosts (e.g. humans) have chronic viral and parasitic infections with no evidence of disease. Indeed, there are now examples of complex interactions between these microbes and hosts that seem to confer an advantage to the host at a particular time, suggesting that the relationship has progressed along an axis from parasitic to commensal to one of a mutualistic symbiosis. This concept is explored using examples from viruses and parasites, considering how the relationships may be not only detrimental but also beneficial to the human host. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play a variety of roles in diverse biological processes at the post-transcriptional regulatory level. Although numerous miRNAs have been identified in parasitic helminths, we still know little about their biological functions. As molecular signatures that can be stably detectable in serum and plasma, worm-derived miRNAs have shown promise as markers for the early detection of particular helminth infections. In addition, host miRNAs are dysregulated during the development of pathology associated with helminthiases and show potential as therapeutic intervention targets. This review discusses the possible biological roles of helminth miRNAs, the prediction of their specific targets, their application in diagnosis and anti-pathology therapy interventions, and the potential functions of miRNAs in extracellular vesicle cargo, such as exosomes, in helminth–host interplay. [ABSTRACT FROM AUTHOR]

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. [ABSTRACT FROM AUTHOR]

Sheep play an important role in national economy and social economy in rural areas in Iran. The main goal of this study was to investigate the fauna and frequency of parasitic helminth infections prevalent in native sheep in Hamedan, western Iran. From April 2010 to March 2011, the gastrointestinal and respiratory tracts of 100-sheep were examined using conventional parasitological methods. The overall infection rate was found as 69%. No infection was found in esophagus and rumens. Parabronema skerjabini (22%) and Ostertagia circumcincta (1%) were recorded as the maximum and minimum cases for the presence of nematode, respectively. On the other hand, the most dominant of trematode and cestode were Fasciola hepatica (13%) and Monezia expansa (13%), respectively. The highest infection rate was reported in summer (84%). The prevalence of helminth infection was varied among gender, seasons and age groups. In conclusion, this is the first report of parasitic helminth infections in sheep in Hamedan province in western Iran. Our results provide baseline information for the future studies. [ABSTRACT FROM AUTHOR]

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed. [ABSTRACT FROM AUTHOR]

ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, exhibits anti-inflammatory properties by virtue of covalently attached phosphorylcholine moieties. Screening of a library of ES-62 phosphorylcholine-based small molecule analogues (SMAs) revealed that two compounds, termed 11a and 12b, mirrored the helminth product both in inhibiting mast cell degranulation and cytokine responses in vitro and in preventing ovalbumin-induced Th2-associated airway inflammation and eosinophil infiltration of the lungs in mice. Furthermore, the two SMAs inhibited neutrophil infiltration of the lungs when administered therapeutically. ES-62-SMAs 11a and 12b thus represent starting points for novel drug development for allergies such as asthma. [ABSTRACT FROM AUTHOR]