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The NapA protein of B. burgdorferiis essential for the persistence of spirochetes in ticks. One of the most intriguing aspects of NapA is its potential to interfere with the host immune system. Here, we investigated the role of the acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced in microglia cells and CSF T cells following NapA stimulation. We report here that NapA induced a regulatory T (Treg) response in the CSF of patients with chronic Lyme borreliosis and it is able to expand this suppressive response by promoting the production of TGF-ß and IL-10 by microglia cells. Collectively, these data strongly support a central role of NapA in promoting both Treg response and immune suppression in the CSF of patients with chronic Lyme borreliosis and suggest that NapA and the Treg pathway may represent novel therapeutic targets for the prevention and treatment of the disease.

There is a need for updated guidance on detection, management and surveillance of sexually transmitted infections (STIs). Chlamydia, gonorrhoea and syphilis reporting needs to be mandatory in more European countries to aid collection of data. More widespread Chlamydia screening is needed in many countries as this is the only way to reduce complications. The role of Human Papillomavirus (HPV) screening in a situation where the prevalence of HPV infection has dropped significantly was also discussed in the context of the high cost of screening, the need for a relatively complex infrastructure, particularly in developing countries, and falling vaccination costs. An integrated HPV vaccination and screening policy could be the most appropriate with vaccination at 9–13 years as recommended by WHO and a single HPV screen at 35–39 years, possibly repeated thereafter every 10 years. Female and male HPV vaccination programmes could lead to near elimination of genital warts in both females and males. Surveillance of STIs should be intensified where needed; additional or better quality data should be collected including reasons for testing, denominator data to estimate positivity rates, diagnostic methods, concurrent STIs, sexual orientation and country of acquisition; more analytical rather than descriptive epidemiology is needed.

Helicobacter pyloriinfection induces a chronic gastric inflammatory infiltrate. This study was undertaken to evaluate the type of the innate immune responses elicited by the secreted peptidyl-prolyl cis-trans isomerase of H. pylori(HP0175). The cytokine production induced by HP0175 in neutrophils, and monocytes was evaluated. HP0175 was able to induce the expression of IL-23 in neutrophils, and monocytes, and IL-6, IL-1beta and TGF-beta in monocytes. These findings indicate that HP0175 is able to promote the activation of innate cells and the production of a cytokine milieu that may favour the development of Th17 response.

Th2 responses seem to play an important role in defence against Trichinella spiralis(Ts). The Neutrophil Activating Protein of Helicobacter pylori(HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitrowas used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p< 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r −0.617, p= 0.0013 and HP-NAP-treated: r −0.678, P= 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r −0.390, P= 0.0592 and r −0.803, P= 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivoby HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.

Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamianaadministered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent Y. pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-α, IL-12, IL-10, IL-1β, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from Y. pestisinfection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y. pestisinfection.

Background & Aims: Neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma are responsive to T helper cells and sensitive to withdrawal of H. pylori-induced T-cell help. Methods: The clonal progeny of T cells from the gastric mucosa of 5 patients with MALT lymphoma was compared with that of T-cell clones obtained from 5 H. pylori-infected patients with chronic gastritis. Results: T-cell clones were assessed for specificity to H. pylori, cytokine profile, help for B-cell proliferation, and perforin- or Fas-mediated cytotoxic regulation of B-cell growth. Twenty-eight of 165 CD4^+ gastric clones from MALT lymphoma and 33 of 178 CD4^+ clones from chronic gastritis recognized H. pylori antigens. Cytokine production was similar in the 2 series of clones. All MALT lymphoma-derived clones dose-dependently increased their B-cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1 because of concomitant cytolytic killing of B cells. T-cell clones from MALT lymphoma had both reduced perforin-mediated cytotoxicity and poor ability to induce Fas-mediated apoptosis. These defects were limited to gastric T cells. Conclusions:H. pylori-induced T cell-dependent B-cell activation and deficient cytotoxic control of B-cell growth may link H. pylori infection, local T-cell response, and genesis of low-grade gastric MALT lymphoma. GASTROENTEROLOGY 1999;117:1105-1112

Background: Increasing evidence shows that nerve growth factor (NGF) plays a role in the complex and fascinating linkage between the nervous and the immune systems due to its ability to modulate functions of several inflammatory cells. Objective: To investigate NGF receptor expression and NGF production and release by human CD4+ cells clones, which have primary relevance in modulating inflammatory events through their different subsets of functional phenotypes. Methods: The expression of NGF and a transmembrane tyrosine kinase (TrkA) was evaluated by immunohistochemistry and flow cytometry analysis in five T"H"0, six T"H"1, and five T"H"2 cell clones derived from human circulating mononuclear blood cells. Moreover, the amount of NGF protein was assessed by measuring the NGF levels in culture supernatants of the T cell clones before stimulation and 48 hours after phytohemagglutinin (PHA) activation by use of an immunoenzymatic assay. Results: Our data have shown that in unstimulated conditions, human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile. Moreover, T"H"1 and T"H"2 clones, but not T"H"0 clones, secrete NGF in basal conditions. PHA activation induces NGF secretion in T"H"0 clones and a significant increase of NGF levels in T"H"2 (p < 0.05), but not in T"H"1 culture supernatants. Conclusions: Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network. (J Allergy Clin Immunol 1997;100:408-14.)