Th1 and Th2 cytokines in mice with invasive aspergillosis

With a murine model of invasive aspergillosis we investigated cytokine production by CD4+ T helper cells and the effects of cytokine administration or neutralization on the course and outcome of infection. Patterns of susceptibility and resistance to infection were obtained with different strains of mice injected with different inocula of Aspergillus fumigatus conidia. Mice surviving the primary infection also resisted a subsequent lethal infection that was associated with production of gamma interferon by CD4+ T splenocytes. Impaired neutrophil antifungal activity, observed in susceptible mice, was concomitant with a predominant production of interleukin-4 (IL-4) by CD4+ splenocytes. In these mice, exogenous administration of IL-12 failed to induce resistance to infection; in contrast, treatment with soluble IL-4 receptor cured more than 70% of the mice from primary infection and resulted in the onset of acquired resistance to a subsequent lethal infection. These findings indicate that in murine invasive aspergillosis, production of IL-4 by CD4+ T cells may be one major factor discriminating susceptibility and resistance to infection.