CD4+ T cell-mediated fatal hyperinflammatory reactions in mice infected with Penicillium marneffei

Abstract

SUMMARYIn the present study, we demonstrate that all mice survived when a low dose of Penicillium marneffei was instilled intratracheally, while severe infection induced by instillation of 1 × 10 8 and 1 × 10 7 colony-forming units (CFU) killed all and 50% of mice, respectively, within 14 days, although the number of live microorganisms in the lungs of these animals was found to decrease with time. The cellular inflammatory responses in the lungs were much more striking in mice with severe infection than in animals infected with a low dose of microorganisms. The number of leucocytes, macrophages, neutrophils and lymphocytes in the lungs increased progressively during infection, and were more than 50 times higher on day 11 than in the control count. CD4 þ T cells were the predominant cells in the lungs, and played an important role in hyperinflammatory host reactions, because neutralizing anti-CD4 MoAb increased the survival rate in infected mice despite the presence of a high number of live microorganisms in the lungs. Our results indicate that severe infection with P. marneffei induces fatal hyperinflammatory host reactions, mediated to a large extent by CD4 þ T cells, although the infection is well controlled. However, the contribution of endogenous tumour necrosis factor-alpha (TNF-a) remains unsubstantiated, since administration of neutralizing anti-TNF-a MoAb in the present study failed to prolong survival in infected mice.

Different susceptibilities of yeasts and conidia ofPenicillium marneffeito nitric oxide (NO)-mediated fungicidal activity of murine macrophages

“…A clinical strain of P. marneffei, designated H1140 [36], was recently registered by American Type Culture Collection (ATCC 201013). The method of preparation of conidial suspensions was described in our previous study [36].…”

“…A clinical strain of P. marneffei, designated H1140 [36], was recently registered by American Type Culture Collection (ATCC 201013). The method of preparation of conidial suspensions was described in our previous study [36]. For preparing inocula of yeast cells, conidia were incubated in brain heart infusion broth (BHI; Eiken) at 37ЊC for 7-14 days, as described in a previous study [37].…”

Thermally Dimorphic Human Fungal Pathogens—Polyphyletic Pathogens with a Convergent Pathogenicity Trait

“…Untreated disseminated disease is often fatal. Experiments in mice have shown that, in the absence of immunosuppression, infections with high numbers of conidia (4 Â 10 5 ) are eventually cleared, whereas athymic mice die from the infection (Kudeken et al 1997). This shows that immune status of the host is a key factor in the outcome of infection.…”