Cytokine response to Cryptococcus neoformans in murine pulmonary infection

C. neoformans is an encapsulated fungus that causes meningitis in patients with AIDS. The lung is the portal of entry of C. neoformans in humans. The effective tissue response for controlling infection is granulomatous inflammation, but the signals required to produce this response are unknown. Administration of an anticapsular IgG1 mAb to mice infected experimentally results in an enhanced granulomatous response We studied the cytokine response to C. neoformans infection. A/JCr mice were infected intratracheally (i.t.) with 10⁴ C neoformans ATCC strain 24067. MAb-treated mice received 1.5 mg of purified mAb 2H1 intraperitoneally (i.p.) one day prior to infection & control mice received PBS i.p. Naive & sham-infected mice were also studied. Mice were killed 1, 2, 4, 7 and 14 d after infection. RNA was extracted from lung and reverse transcribed to cDNA. Quantitative PCR was done for IL-2, IL-4, IL-10, IL-12 and IFN-γ mRNA expression. CPUs from 10% of the lung confirmed infection. On days 4 and 7 of infection, IL-4 and IFN-γ mRNA are detectable. At day 7, mRNA for IL-10 and, in some mice, IL-12 are expressed above the basal level seen in naive and sham-infected mice. Expression of mRNA for IL-2 was not detected during the first 14 days of infection. Preliminary data suggests that there may be a quantitative reduction in the expression of T_H2-assoaated cytokines in mice treated with mAb. We conclude that: i.) cytokine expression occurs early in the course of infection; ii.) both T_H1- and T_H2-assodated cytokine mRNAs are expressed in mice infected i.t. with C. neoformans; iii.) there appears to be a trend towards the development of a T_H2 response; iv.) antibody administration may change either the temporal or quantitative expression of some cytokines.