Neutrophils modulate the immune response to Cryptococcus neoformans 3456

Description Cryptococcus neoformans infections are a significant cause of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. There are an estimated quarter million cases of cryptococcal meningitis each year, resulting in 200,000 deaths. Neutrophils are essential in the protective immune response to most Candida and Aspergillus. However, neutropenia is not a risk factor for developing cryptococcosis. The role of neutrophils has been insufficiently explored in response to C. neoformans, but there exists evidence for both helpful and harmful roles in cryptococcal infections. We initially sought to define the role of neutrophils in the immune response to C. neoformans by first depleting neutrophils. It was previously reported that neutrophil depletion leads to increased mouse survival. To our surprise, the neutrophil-depleted mice succumbed to the infection faster than the controls. Mortality was not due to changes in fungal burden, suggesting that death was host-mediated. Additionally, mortality was not dependent on the mouse background. Cytokine and flow cytometry analysis found that deletion of neutrophils induces a strong proinflammatory immune response, with changes in recruitment and ratios of multiple monocyte subsets. Neutrophil depletion also decreases the Th2-type cytokine levels. Altogether, our data indicate that neutrophils play a role in modulating the cryptococcal immune response.