Differential mechanisms of resistance to sublethal systemic Aspergillus fumigatus infection in immunocompetent BALB/c and C57BL/6 mice

Department of Ecology, University of Belgrade, Institute for Biological Research Sinisa Stankovic, Bulevar despota Stefana 142, Belgrade, Serbia.
Immunobiology (Impact Factor: 3.04). 01/2010; 216(1-2):234-42. DOI: 10.1016/j.imbio.2010.04.007
Source: PubMed


Studies of systemic and pulmonary Aspergillus fumigatus infection demonstrated differential susceptibility of inbred mice of various genetic background to lethal outcome, with an opposite pattern of Th1 cytokine interferon-γ (IFN-γ) and Th2 cytokine interleukin-4 (IL-4) in susceptible vs resistant mice. We have shown recently reciprocal IFN-γ and IL-4 expression in spleens of Th1-prone C57BL/6 mice in sublethal systemic aspergillosis. In this study, resistance to systemic (i.v.) A. fumigatus infection was investigated in Th2-prone BALB/c mice by survival rate at different fungal inocula, efficiency of reduction of visceral organ and spleen fungal burden at sublethal conidia dose and splenic immune response to this dose and compared to C57BL/6 mice. No strain differences in survival were noted at three A. fumigatus doses, with similar extent and dynamics of fungal eradication from all organs following sublethal conidia dose injection. Progressive decrease in spleen fungal burden was associated with different dynamics and quality of changes in spleen activity of BALB/c and C57BL/6 mice. Increased spleen mass and cellularity was noted in both strains, with higher values in BALB/c mice at some time points what might be ascribed to peripheral blood cell recruitment, as well as hematopoietic activity and red pulp upgrowth. Infection tipped the balance towards pro-inflammatory antifungal splenic response by a highly increasing IFN-γ and without changing the IL-4 expression in BALB/c mice, in contrast to down-regulating anti-inflammatory (IL-4) and a moderately increasing IFN-γ response in C57BL/6 mice. Jointly, stimulation of IL-17 expression noted in both strains provided an optimal inflammatory milieu in the spleen of infected mice that might have contributed to efficient removal of conidia.

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    • "In contrast to the increase of IFN-␥ in WT mice, which confirms our previous findings concerning this cytokine in sublethal systemic aspergillosis in immunocompetent C57BL/6 mice (Mirkov et al. 2010, 2011), the lower production and expression of IFN-␥ in MIF −/− compared to WT mice, imply Th1 promoting activity of MIF in systemic Aspergillus infection. This is in line with the pro-inflammatory activity of MIF during protection against bacterial infections (Koebernick et al. 2002) and in a wider context with data that MIF is equally efficiently involved in the adaptive immune response through favouring Th1 activation and differentiation (Cvetkovic and Stosic-Grujicic 2006; Koebernick et al. 2002). "
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