EVOLUTION OF THE PRIMARY IMMUNE-RESPONSE TO HISTOPLASMA-CAPSULATUM INMURINE LUNG

Histoplasma capsulatum induces a cell mediated immune response in the lungs and lymphoid organs of mammals, In this study, we analyzed the p rogression of the cytokine and inflammatory reactions in the lungs of mice infected intranasally with H. capsulatum. We measured cytokine mR NA levels and determined the inflammatory cell populations during the active phase of infection (<3 weeks). Transcription of genes encoding interleukin-2 (IL-2), IL-4, and IL-12 and gamma interferon (IFN-gamma) was detectable as early as day 3 of infection, whereas a signal for I L-IO was never observed, Competitive PCR analysis demonstrated that en hanced expression of IL-12 mRNA was observed by day 3 and that express ion of mRNA for IL-2 and IFN-gamma progressively increased from day 5 to day 10. All levels declined by day 14, Analysis of the inflammatory response revealed an initial elevation in myeloid cells (Mac-1(+)) an d natural killer (NK) cells followed by a rise in T cells, predominant ly CD4(+) cells, Since IFN-gamma is a key factor in host defense, we p erformed cytoplasmic staining to determine the cell populations that p roduced this cytokine. The hierarchy of synthesis was CD4(+) > CD8(+) > NK cells, Thus, H, capsulatum provokes an orderly modulation of the inflammatory and cytokine responses in murine lungs.