Differential mechanisms of resistance to sublethal systemic Aspergillus fumigatus infection in immunocompetent BALB/c and C57BL/6 mice.
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.
Mirkov
Ivana
I
Department of Ecology, University of Belgrade, Institute for Biological Research Sinisa Stankovic, Bulevar despota Stefana 142, Belgrade, Serbia.
Stojanovic
Ivana
I
Glamoclija
Jasmina
J
Stosic-Grujicic
Stanislava
S
Zolotarevski
Lidija
L
Kataranovski
Dragan
D
Kataranovski
Milena
M
D000818:Animals; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D007110:Immunity, Active; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D016207:Cytokines