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Recognition of pathogen‐associated molecular patterns (PAMPs) through Toll‐like receptors (TLRs) plays a pivotal role in first‐line pathogen defense. TLRs are also likely triggered during a Plasmodium infection in vivo by parasite‐derived components. However, the contribution of innate responses to liver infection and to the subsequent clinical outcome of a blood infection is not well understood. To assess the potential effects of enhanced TLR‐signalling on Plasmodium infection, we systematically examined the effect of agonist‐primed immune responses to sporozoite inoculation in the P. berghei/C57Bl/6 murine malaria model. We could identify distinct stage‐specific effects on the course of infection after stimulation with two out of four TLR‐ligands tested. Priming with a TLR9 agonist induced killing of pre‐erythrocytic stages in the liver that depended on macrophages and the expression of inducible nitric oxide synthase (iNOS). These factors have previously not been recognized as antigen‐independent effector mechanisms against Plasmodium liver stages. Priming with TLR4 and ‐9 agonists also translated into blood stage‐specific protection against experimental cerebral malaria (ECM). These insights are relevant to the activation of TLR signalling pathways by adjuvant systems of antimalaria vaccine strategies. The protective role of TLR4‐activation against ECM might also explain some unexpected clinical effects observed with pre‐erythrocytic vaccine approaches. [ABSTRACT FROM AUTHOR]

Immunity to intestinal nematodes requires CD4⁺ Th2-cell responses, including IL-4 and IL-13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection. While both tissue-resident memory (TRM) populations proliferate in situ and express IL-4, IL-5, and IL-13 upon TCR-dependent stimulation, only peritoneal memory cells express high levels of the IL-33 receptor and produce IL-5 and IL-13 upon TCR-independent stimulation with IL-33 and IL-7. Most importantly, PC-derived TRM cells are able to mediate anti-helminthic effects by decreasing the fecundity of female worms upon transfer into recipient mice. These results show that nonlymphoid compartments can serve as reservoirs for Th2 memory cells, and furthermore that innate effector function of Th2 memory cells is restricted to CD4⁺ memory T cells residing in the PC. [ABSTRACT FROM AUTHOR]

Immunity to intestinal nematodes requires CD4⁺ Th2-cell responses, including IL-4 and IL-13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection. While both tissue-resident memory (T RM ) populations proliferate in situ and express IL-4, IL-5, and IL-13 upon TCR-dependent stimulation, only peritoneal memory cells express high levels of the IL-33 receptor and produce IL-5 and IL-13 upon TCR-independent stimulation with IL-33 and IL-7. Most importantly, PC-derived T RM cells are able to mediate anti-helminthic effects by decreasing the fecundity of female worms upon transfer into recipient mice. These results show that nonlymphoid compartments can serve as reservoirs for Th2 memory cells, and furthermore that innate effector function of Th2 memory cells is restricted to CD4⁺ memory T cells residing in the PC., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)