CD4, but not Cxcr6, is necessary for control of Pneumocystis murina infection.

Abstract

CD4+ T cells are critical to control of Pneumocystis infection, and Cxcr6 has been shown to be upregulated in these cells during infection, but the roles of CD4 and Cxcr6 in this setting are undefined. To explore this, mice deficient in CD4 or Cxcr6 expression were utilized in a co-housing mouse model that mimics the natural route of Pneumocystis infection. Organism load and anti-Pneumocystis antibodies were assayed over time, and immunohistochemistry, flow cytometry, and quantitative PCR were used to characterize host immune responses during infection. CD4 was found to be necessary for clearance of Pneumocystis murina, though partial control was seen in it's absence; based on ThPOK expression, double negative T cells with T helper cell characteristics may be contributing to this control. Using a Cxcr6 deficient mouse expressing gfp, control of infection in the absence of Cxcr6 was similar to that in heterozygous control mice. It is noteworthy that gfp + cells were seen in the lungs with similar frequencies between the 2 strains. Interferon-ɣ and chemokine/ligands Cxcr3, Cxcl9, and Cxcl10 increased during P. murina infection in all models. Thus, CD4, but not Cxcr6, is needed for clearance of P. murina infection.