Experimental Leishmania major infection in mice: role of IL‐10

Abstract

L. major infection of mice induces polarized Th1 and Th2 responses that are correlated with healing of the infection (Th1) or a fatal disease (Th2). The Th subset specific cytokines, IFNgamma and IL-4, themselves were shown to be important factors for the differentiation into the Th1 and Th2 pathways during infection. We studied the role of the Th2 cytokine IL-10 during leishmania infection: removal of endogenous IL-10 by anti-IL-10 treatment did not alter the Th2 cytokine pattern in non-healer mice nor did it modulate DTH reactivity, IgE production or fatal disease progression, but partially blocked the IFNgamma inhibiting effect of rIL-4 in healer mice. During chronic infection similar amounts of IL-10 were produced in both healer and non-healer mice. However, at early time-points during infection IL-10 production was significantly higher in the non-healer Th2 responder animals. IL-10 production in vitro caused significant inhibition of in vitro IFNgamma production. In conclusion IL-10, unlike IL-4 and IFNgamma, does not seem to play a readily detectable role in the Th subset differentiation during L. major infection. However, the high production of IL-10 early during infection in non-healer mice and inhibition of leishmania-specific IFNgamma production may contribute to drive the immune response towards a Th2 response.

Th1/Th2 immune responses are associated with active cutaneous leishmaniasis and clinical cure is associated with strong interferon-γ production

“…IL-10 plays an important role in the regulation of the immune response, mainly by inhibiting IFN-␥ synthesis and macrophage activation. Experimental models of Leishmania infection have shown that initial IL-10 production by susceptible mouse strains inhibited IFN-␥ production and contributed to L. (L.) major escape and maintenance of infection [27]. Recently it was observed that the lack of IL-10 promoted parasite elimination and clinical cure of animals infected with an extremely virulent L. (L.) major strain [15,28], although complete parasite elimination in the absence of IL-10 activity causes the loss of immunity to reinfection, thus suggesting that IL-10 is involved both in disease progression, when produced at high levels, and in the development of memory T cells, when produced at low levels [29].…”

Immunologic influences on allergy and the TH1/TH2 balance

“…30 However, the same cytokine appears to drive the immune response toward a T H 2 phenotype in Leishmania major infection. 31 More importantly, disruption of the IL10 gene resulted in a significant increase in IFN-γ but reduced secretion of IL-4 and prevented skin eosinophilia in a murine model of allergic dermatitis, suggesting a favoring rather than suppressive role for this cytokine in allergic inflammation. 32 These discordant effects of IL-10 might obviously be due to the genetic background because IL-10-dependent events in mice are strongly strain dependent.…”

Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies

“…IL-10 gene deficient mice are highly resistant to L. major [27], and over expression of IL-10 renders resistant mice susceptible [28]. In addition to deactivating macrophages and inhibiting intracellular parasite killing, IL-10 also directly inhibits the development of Th1 cells and their production of IFN-c [29,30]. Recently, IL-10 produced by natural CD4+CD25+ regulatory T cells has been shown to play an important role in disease chronicity [31,32].…”