CCR2 expression determines T1 versus T2 polarization during pulmonary Cryptococcus neoformans infection

Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requi res the development of T1-type immunity. The objective of this study was to determine the role of CCR2 in leukocyte recruitment and development of T1- type cell-mediated immunity during pulmonary C, neoformans infection. Intra tracheal inoculation of C. neoformans into CCR2 knockout (CCR2(-/-)) mice p roduced a prolonged pulmonary infection (5000-fold CFU at 6 wk compared wit h CCR2(+/+) mice) and significant dissemination to the spleen and brain (16 0- and 800-fold greater). In addition, CCR2 deficiency resulted in signific antly reduced recruitment of macrophages (weeks 1-3) and CD8(+) T cells (we eks 1-2) into the lungs. The immune response in CCR2(-/-) mice was characte rized by chronic pulmonary eosinophilia, crystal deposition in the lungs, p ulmonary leukocyte production of IL-4 and IL-5 but not IFN-gamma, lack of a nticryptococcal delayed-type hypersensitivity, and high levels of serum IgE , These results demonstrate that expression of CCR2 is required for the dev elopment of a T1-type response to C. neoformans infection and lack of CCR2 results in a switch to a T2-type response. Thus, CCR2 plays a critical role in promoting the development of T1- over T2-type immune responses in the l ung following cryptococcus infection.