Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice

Abstract

Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) play an important role in the recruitment of PMNs at the site of invasive Candida infection. In the absence of either TNFalpha or IL-6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G-CSF (rG-CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicans from the organs of rG-CSF-treated mice is significantly decreased. Treatment with the combination of rG-CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candida infection, rG-CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life-threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candida infection.

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…At 48 h post-challenge, they found an increase in the number of total cells, mainly due to PMN leukocytes influx in the BAL fluid. These results are consistent with other experimental models using medical important fungi such as Candida albicans, Aspergillus fumigatus and Pneumocystis carinii [56][57][58][59], where it has been demonstrated that the recruitment of PMNs occurs during first day post-challenge, and that this recruitment is mediated by pro-inflammatory cytokines including TNF-a, IL-6, IL-1b and granulocyte-macrophage colony stimulating factor (GM-CSF). As described below, in this model of pulmonary PCM, Fig.…”

Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses byAspergillus fumigatus

“…Cortez et al showed that conidia can induce differential expression of genes implicated in host defense and immunomodulation (5). The diminished IL-6 and IL-1␤ response reported in our study may be biologically significant as these cytokines orchestrate the host proinflammatory antimicrobial response, including neutrophil recruitment (14,39). In addition, altered levels of these proinflammatory cytokines affect the Th1-Th2 equilibrium, which may result in an attenuated host phagocytic and cytotoxic response (33).…”

Interplay between Candida albicans and the Mammalian Innate Host Defense

“…In addition to proinflammatory cytokines, the hematopoietic growth factors granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are critical for recruitment and activation of PMNs (51,54). In addition to their direct killing of C. albicans, it was demonstrated that PMNs are the only cell type in blood which can inhibit C. albicans germ tube formation (33).…”