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Introduction: Intestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known. Results: Using a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/ hyperplasia, and elevated levels of Adamts gene expression. Discussion: To our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost. [ABSTRACT FROM AUTHOR]

This document is a corrigendum published in the journal Frontiers in Immunology. It corrects errors in a previously published article titled "Trickle infection with Heligmosomoides polygyrus results in decreased worm burdens but increased intestinal inflammation and scarring." The errors include incorrect numbers in Figure 1 and an incorrect statement about cell numbers in the results section. The authors apologize for the errors and state that they do not change the scientific conclusions of the article. The original article has been updated. [Extracted from the article]

Abstract Background The porcine roundworm Ascaris suum impairs feed conversion and weight gain, but its effects on intestinal microbiota remain largely unexplored. Methods Modulation of the intestinal microbiota was assessed in pigs that were infected once with 10,000 A. suum eggs and pigs that received a trickle infection (1000 eggs/day over 10 days), compared with a non-infected control group. Six pigs each were sacrificed per group at days 21, 35 and 49 post-infection (p.i.). Faecal samples taken weekly until slaughter and ingesta samples from different intestinal compartments were subjected to next-generation sequencing of the bacterial 16S rRNA gene. Results The results revealed marked differences between the single- and the trickle-infected group. Single infection caused a remarkable but transient decrease in microbial diversity in the caecum, which was not observed in the trickle-infected group. However, an increase in short-chain fatty acid-producing genera in the caecum on day 21 p.i., which shifted to a decrease on day 35 p.i., was common to both groups, possibly related to changes in excretory–secretory products following the parasite’s final moult. Faecal microbial interaction networks were more similar between the single-infected and control group than the trickle-infected group. In addition, a lower degree of similarity over time indicated that A. suum trickle infection prevented microbiota stabilization. Conclusions These different patterns may have important implications regarding the comparability of experimental infections with natural scenarios characterized by continuous exposure, and should be confirmed by further studies. Graphical Abstract

IntroductionIntestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known.ResultsUsing a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels of Adamts gene expression.DiscussionTo our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost.

Background: The porcine roundworm Ascaris suum impairs feed conversion and weight gain, but its effects on intestinal microbiota remain largely unexplored. Methods: Modulation of the intestinal microbiota was assessed in pigs that were infected once with 10,000 A. suum eggs and pigs that received a trickle infection (1000 eggs/day over 10 days), compared with a non-infected control group. Six pigs each were sacrificed per group at days 21, 35 and 49 post-infection (p.i.). Faecal samples taken weekly until slaughter and ingesta samples from different intestinal compartments were subjected to next-generation sequencing of the bacterial 16S rRNA gene. Results: The results revealed marked differences between the single- and the trickle-infected group. Single infection caused a remarkable but transient decrease in microbial diversity in the caecum, which was not observed in the trickle-infected group. However, an increase in short-chain fatty acid-producing genera in the caecum on day 21 p.i., which shifted to a decrease on day 35 p.i., was common to both groups, possibly related to changes in excretory–secretory products following the parasite's final moult. Faecal microbial interaction networks were more similar between the single-infected and control group than the trickle-infected group. In addition, a lower degree of similarity over time indicated that A. suum trickle infection prevented microbiota stabilization. Conclusions: These different patterns may have important implications regarding the comparability of experimental infections with natural scenarios characterized by continuous exposure, and should be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity in natura is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of “trickle” infections to experimentally model the kinetics of natural infection.

Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity in natura is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of "trickle" infections to experimentally model the kinetics of natural infection. [ABSTRACT FROM AUTHOR]

This study investigated the changes in establishment rates during the time course of a 6 week trickle infection of chickens with Ascaridia galli at two different dose levels, using a molecular marker. To differentiate early and late infection, two different egg cohorts (haplotype a and haplotype b , genetically identified using PCR-linked restriction fragment length polymorphism on the cox 1 gene of the mitochondrial DNA) were used. Cohort-specific egg batches were produced by harvesting eggs from the uteri of female worms of the specific cohort. Fifty-six 8 week old Lohmann Brown Lite chickens were divided into seven groups and the infectivity of the egg batches was compared between two groups of chickens ( P = 0.6). The remaining chickens were allocated to four infection regimes and one control group. Group ab100 was trickle infected for 3 weeks with 100 eggs of haplotype a (twice weekly) followed by the same dose of eggs of haplotype b for another 3 weeks. Group ba100 was treated similarly but in the opposite order (haplotype b preceding a ). A similar infection regime was applied for groups ab25 and ba25 but with a lower inoculation dose (25 eggs). All of the birds in these five groups (four infected and one control) were euthanased 2 weeks after the last inoculation. It was found that in the low-dose groups both the early and late infections established equally well, whereas in the high-dose groups the early infection was recovered in a significantly ( P < 0.001) higher proportion of chickens than the late infection, irrespective of genetic cohorts. Moreover, relatively higher proportions of the larvae from both the early and late infections were found in the posterior section of the small intestine. This result indicates the presence of dose-dependent resistance against reinfection and this resistance seems to act by reducing the establishment of late infection and by relocating the larvae from early infection. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus , the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known., Results: Using a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels of Adamts gene expression., Discussion: To our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ariyaratne, Kim, Pollo, Perera, Liu, Nguyen, Leon Coria, de Cassia Luzzi, Bowron, Szabo, Patel, Wasmuth, Nair and Finney.)

Abstract: A study was conducted to assess the growth performance and nutrient utilisation of crossbred calves trickle infected with Fasciola gigantica (F. gigantica) and/or supplemented with deoiled mahua (Bassia latifolia) seed cake (DMSC) during patent period of infection. Twenty healthy crossbred (HF X Haryana) male calves aged 6–7 months with an initial average live weight of 79.59±2.71kg were divided into four treatment groups (CON, CON–INF, DMC and DMC–INF) of 5 animals each following randomized block design. DMSC was included in the concentrate mixture of DMC and DMC–INF groups at 100g/kg. Animals of groups CON–INF and DMC–INF were given an infection of 200 metacercariae (mc) of F. gigantica as trickle infection dose of 50 mc twice weekly over a period of two weeks. A metabolism trial at 105–114 days post infection (DPI) and growth trial of 172 day duration were conducted. Calves under CON–INF exhibited significantly lower (P<0.05) body weight gain and average daily gain (ADG) accompanying poorer feed conversion efficiency (FCE) as compared to others, whereas the body weight gain and ADG were significantly (P<0.05) higher in DMC–INF group. The intake and digestibility of nutrients were not affected (P>0.05) by trickle infection with F. gigantica. However, higher urinary excretion of nitrogen and lower (P<0.01) nitrogen balance were observed in CON–INF group as compared to other three groups. The nitrogen balance was improved (P<0.01) in DMC–INF group. The urinary and faecal excretion of calcium (P<0.01) and urinary excretion of phosphorus (P<0.001) were higher in both the infected groups contributing to a lower balance of these minerals in the infected groups. Serum total protein and albumin concentration of CON–INF group were significantly (P<0.001) lower as compared to other groups, whereas it was improved in DMC–INF group. The A:G ratio in the infected groups showed a decreasing trend from 30 DPI. Serum glucose concentration remained unaffected due to infection/supplementation. The study concluded that the supplementation of deoiled mahua seed cake at 100g/kg level in the concentrate mixture could improve the growth performance and nitrogen utilisation of F. gigantica trickle infected crossbred calves. [Copyright &y& Elsevier]