T‐cell‐derived, but not B‐cell‐derived, IL‐10 suppresses antigen‐specific T‐cell responses in <i>Litomosoides sigmodontis</i>‐infected mice

Haben, Irma; Hartmann, Wiebke; Specht, Sabine; Hoerauf, Achim; Roers, Axel; Müller, Werner; Breloer, Minka

doi:10.1002/eji.201242929

Cited by 17 publications

(15 citation statements)

References 31 publications

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“…This suggests that immune modulation during acute and chronic L. sigmodontis infection in C57BL/6 and BALB/c mice is established by similar mechanisms such as IL-10 induction [31]. Potential mediators of suppression in addition to Foxp3 + T reg are IL-10 producing Foxp3 − T cells [50], IL-10 producing regulatory B cells [51], [52], alternatively activated macrophages [53], and tolerogenic dendritic cells [54] that have been shown to mediate suppression during nematode infection in several murine systems. We are currently testing the function of these regulatory cell populations in suppression of OT-II T cell proliferation during acute L. sigmodontis -infection of C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 93%

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

2014

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One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections.

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Section: Discussionmentioning

confidence: 93%

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

2014

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“…Despite abundant expression of the IL-10 receptor, YM1, RELMa, arginase and many other AA markers, RNAseq analysis of nematode-elicited macrophages had sufficient depth of coverage to be able to say that IL-10 is not produced by F4/80hi macrophages in this context (9). The important source of IL-10 following both hookworm migration through the lung and filarial nematode infection appears to be T cells (146,158). This is consistent with recent data showing anti-inflammatory functions of gut macrophages are mediated not by their ability to produce IL-10 but by IL-10 receptor expression (159).…”

Section: Suppressing Inflammationmentioning

confidence: 99%

Macrophage proliferation, provenance, and plasticity in macroparasite infection

Rückerl

Allen

2014

Immunological Reviews

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Summary:Macrophages have long been center stage in the host response to microbial infection, but only in the past 10–15 years has there been a growing appreciation for their role in helminth infection and the associated type 2 response. Through the actions of the IL-4 receptor α (IL-4Rα), type 2 cytokines result in the accumulation of macrophages with a distinctive activation phenotype. Although our knowledge of IL-4Rα-induced genes is growing rapidly, the specific functions of these macrophages have yet to be established in most disease settings. Understanding the interplay between IL-4Rα-activated macrophages and the other cellular players is confounded by the enormous transcriptional heterogeneity within the macrophage population and by their highly plastic nature. Another level of complexity is added by the new knowledge that tissue macrophages can be derived either from a resident prenatal population or from blood monocyte recruitment and that IL-4 can increase macrophage numbers through proliferative expansion. Here, we review current knowledge on the contribution of macrophages to helminth killing and wound repair, with specific attention paid to distinct cellular origins and plasticity potential.

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“…As with Hpb infection (15), other helminthic species like Hymenolepis diminuta (16) and Schistosoma mansoni (17) also induce IL10 secretion. Litomosoides sigmodontis suppressed B cells responses in the host through induction of IL10 and Tregs (18, 19). …”

Section: Mechanisms Of Regulationmentioning

confidence: 99%

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

Weinstock

Elliott

2014

The Journal of Immunology

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Helminthic infection has become rare in highly industrialized nations. Concurrent with the decline in helminthic infection is an increase in prevalence of inflammatory disease. Removal of helminths from our environment and their powerful effects on host immunity may have contributed to this increase. Several different helminth species can abrogate disease in murine models of inflammatory bowel disease, type 1 diabetes, multiple sclerosis and other conditions. Helminths evoke immune regulatory pathways often involving dendritic cells, Tregs and macrophages that help control disease. Cytokines such as IL4, IL10 and TGFβ have a role. Notable is helminthic modulatory effect on innate immunity, which impedes development of aberrant adaptive immunity. Investigators are identifying key helminth-derived immune modulatory molecules that may have therapeutic utility in the control of inflammatory disease.

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T‐cell‐derived, but not B‐cell‐derived, IL‐10 suppresses antigen‐specific T‐cell responses in Litomosoides sigmodontis‐infected mice

Cited by 17 publications

References 31 publications

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

Macrophage proliferation, provenance, and plasticity in macroparasite infection

Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

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