Interferon Gamma Inducible Protein 10 (IP-10) and Regulatory T Cells in Leishmaniasis

Abstract

Leishmania are intracellular parasites that reside inside macrophages and induce weak innate immune responses. We hypothesize that transgenic parasites that express immune response genes could modify the nature of the host response to the parasite. We previously generated transgenic parasites that produce interferon gamma inducible protein 10 (IP-10). C57BL/6 mice are resistant to wild type L. major infection but when infected with IP-10 transgenic parasites they develop large lesions in the footpad that do not resolve. Recently it was discovered that nTregs express CXCR3, the receptor for IP-10. We hypothesized that IP-10 transgenic parasites could actively recruit nTregs and thereby enhance parasite persistence. We found higher numbers of CD4+CD25+Foxp3+ cells in the draining lymph nodes of IP-10 parasites infected mice compared to wild type infected mice. This work suggests that IP-10 secreting parasites might recruit a population of regulatory T cells that modulates the immune response to the parasite allowing parasite persistence.