Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to Leishmania donovani infection but develop severe liver immunopathology

The interleukin-27 (IL-27)/T-cell cytokine receptor (TCCR) pathway plays an important role in development of protective immunity against cutaneous leishmaniasis caused by Leisbmania major. in this study, we analyzed the role of IL-27/TCCR pathway in the host defense against visceral leishmaniasis (VL) by monitoring the course of L donovani infection in TCCR-deficient C57BL/6 (TCCR-/-) mice. TCCR-/- mice mounted a robust inflammatory response, produced high levels of pro-inflammatory cytokines, and developed severe liver pathology after L donovani infection that eventually resolved. Interestingly, L donovani-infected TCCR-/- mice controlled the parasite growth in their organs significantly faster than similarly infected TCCR+/+ mice. Adoptive cell transfer and cell depletion studies revealed that CD4(+) T cells were involved in mediating liver immurnopathology and controlling L donovani growth in TCCR-/- mice. These results indicate that the IL-27/TCCR pathway is not essential for the induction of protective Th1 response during VL but is involved in mediating susceptibility to L donovani. Additionally, the data demonstrate that although the IL-27/TCCR interaction limits the severity of liver inflammation during VL by controlling CD4(+) T-cell activity, it is not required for the resolution of hepatic immunopathology.