Differential strain‐related tissue immune response to sublethal systemic Aspergillus fumigatus infection in mice

Abstract

Using a nonlethal systemic Aspergillus fumigatus infection, we have recently shown that similarly efficient elimination of fungus from spleens of prototypic Th1 (C57BL/6) and prototypic Th2 (BALB/c) mice is associated with differential immune responses. In light of these data and given the disseminated character of infection, the aim of the present study is to explore whether there are also strain-dependent differences in antifungal responses in peripheral tissues of infected mice. Although similar efficiency of conidia removal was noted in liver and kidneys of both strains, BALB/c mice seemed more prone to tissue injury. Compared with other nonlymphoid organs, lungs proved immunologically the most responsive in systemic aspergillosis. Lower numbers of neutrophils and macrophages in the lungs of infected BALB/c mice, delayed and lower (compared with C57BL/6 mice) expression of their oxidative activity, along with late IFN-γ and upregulated IL-4 production by lung cells might be responsible for slower elimination of A. fumigatus from the lungs of this mouse strain. The data obtained imply that lungs should be viewed as mandatory organ in evaluation of immune-mediated antifungal potential of drugs in models of systemic/disseminated infection and that strain differences noted in tissue responses should be taken into account in these settings.

Differential Phenotypes of Tissue-Infiltrating T Cells during Angiotensin II-Induced Hypertension in Mice

“…We observed no differences in the amount of cytokines produced from non-infiltrating (blood and spleen) compared to infiltrating T cells. However, there was a predominant Th1 phenotype with greater IFN-γ and TNF-α production, which most likely reflects the C57BL6/J mouse strain [20] , [21] . C57BL6/J mice are also more prone to hypertension and associated systemic and vascular inflammation compared to Th2 prone BALB/c mice, which would further support an association between hypertension and the Th1 phenotype [22] .…”

Effects of intranasally dosed posaconazole on fungal load and biomarkers in Aspergillus fumigatus infected immunocompromised mice

“…In our temporarily neutropenic model, marked production of IL‐17 and IFN‐γ was observed in BALF after A. fumigatus infection (Table and S1). Mirkov et al . also demonstrated changes in pro‐inflammatory cytokines such as IFN‐γ and IL‐17 in A. fumigatus‐ infected mice and rats.…”

“…and S1). Mirkov et al29,30 also demonstrated changes in proinflammatory cytokines such as IFNγ and IL-17 in A. fumigatus-infected mice and rats. Both cytokines, which are components of host anti-fungal defence to A. fumigatus infection, were increased over time up to day 8 postinfection.…”

Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus

“…Similarly, no strain-specific differences in clearance of a sub-lethal fungal dose from liver, kidneys and spleen were observed [83,84], and the lack of difference was attributed to the ability of both strains to increase IFN-γ and IL-17 levels in response to sub-lethal A. fumigatus infection [83]. However, strain-dependent differences were observed in liver injury and fungal clearance from the lungs, after a sublethal systemic A. fumigatus infection [84]. The strain specific differences in the context of pulmonary A. fumigatus infection are not well-established.…”