1887

Abstract

The contribution of reactive oxygen species produced by neutrophils against infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from HO. This study investigated the role of MPO in immunological defence against in an MPO-deficient (MPO) mouse model. The survival of MPO mice infected either intranasally or intravenously with was lower than that of identically challenged wild-type mice. The MPO mice that received intranasal injection of had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)- than wild-type mice, suggesting a weak Th1 response in the MPO mice to . Pathologically, the MPO mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1/ in the lungs. In addition, in MPO mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-derived cytokine (KC) level in the brain of infected MPO mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO mice compared to wild-type, suggesting decreased resistance to not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.

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2006-09-01
2020-01-19
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