The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation
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The protozoan parasite Leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. The immune response associated with healing involves the differentiation of IFNγ-producing Th1 cells, whereas the non-healing phenotype is associated with IL4-producing Th2 cells. The widespread assumption has been that the T-cell differentiation that leads to a healing or non-healing phenotype is established at the time of T-cell activation early after infection. By selectively analyzing the expression of cytokine genes in the T-cell zones of lymph nodes of resistant (Th1) C57BL/6 mice and susceptible (Th2) BALB/c mice during an infection with Leishmania major in vivo, we show that the early T-cell response does not differ between C57BL/6 mice and BALB/c mice. Instead, Th1/Th2 polarization appears suddenly 3 weeks after infection. At the same time point, the number of parasites increases in lymph nodes of both mouse strains, but about 100-fold more in susceptible BALB/c mice. We conclude that the protective Th1 response in C57BL/6 mice is facilitated by the capacity of their innate effector cells to keep parasite numbers at low levels.
KeywordsLeishmania major infection Th1/Th2 cell response In vivo laser microdissection
We thank L. Gutjahr, P. Lau, M.-L. Leppin, K. von Lingelsheim, and S. Möller for technical assistance. Supported by the Deutsche Forschungsgemeinschaft (SFB 654, C4) and the Excellence Cluster “Inflammation at Interfaces” (DFG EXC 306/1) (to JW).