Differential role of NK cells against Candida albicans infection in immunocompetent or immunocompromised mice

Abstract

Little is known regarding the role of NK cells during primary and secondary disseminated Candida albicans infection. We assessed the role of NK cells for host defense against candidiasis in immunocompetent, as well as immunodeficient, hosts. Surprisingly, depletion of NK cells in immunocompetent WT mice did not increase susceptibility to systemic candidiasis, suggesting that NK cells are redundant for antifungal defense in otherwise immunocompetent hosts. NK-cell-depleted mice were found to be protected as a consequence of attenuation of systemic inflammation. In contrast, the absence of NK cells in T/B/NK-cell-deficient NSG (NOD SCID gamma) mice led to an increased susceptibility to both primary and secondary systemic C. albicans infections compared with T/B-celldeficient SCID mice. In conclusion, this study demonstrates that NK cells are an essential and nonredundant component of anti-C. albicans host defense in immunosuppressed hosts with defective T/B-lymphocyte immunity, while contributing to hyperinflammation in immunocompetent hosts. The discovery of the importance of NK cells in hosts with severe defects of adaptive immunity might have important consequences for the design of adjunctive immunotherapeutic approaches in systemic C. albicans infections targeting NK-cell function.Keywords: Candida albicans r host defense r NK cells Additional supporting information may be found in the online version of this article at the publisher's web-site

Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice

“…Consistent to this data, it has been also previously shown that Rag -/-mice clear the primary OPC infection without much immunopathology 27 . Under these conditions, compensatory mechanisms dependent on IL-17A producing innate immune cells have been shown to clear the infection in Rag-/-mice 17,29,30 . Taken together, although IL-17A produced by Th17 cells and neutrophil recruitment are playing a protective role at initial phases of infection, excessive production of TNF-α and other cytokines by Th17 cells, and the continued presence of neutrophils causes exacerbated immunopathology.…”

Host response toCandida albicansbloodstream infection and sepsis

“…157 In a murine model for C. albicans sepsis in immuno-competent mice, NK cells have a detrimental influence on the course of disease by promoting hyper-inflammation, which resulted in reduced survival time. 158 In contrast, in immuno-compromised animals deficient in B and T cells, NK cells were found to be beneficial in recruiting and activating other immune cells, aiding in eventual clearance of the fungus. 158 …”

“…158 In contrast, in immuno-compromised animals deficient in B and T cells, NK cells were found to be beneficial in recruiting and activating other immune cells, aiding in eventual clearance of the fungus. 158 …”

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

“…In a murine model of HDC, the major source of IL-17A was lung ␥␦ T cells, which were required for optimal neutrophil recruitment and control of infection (79). NK cells are not required for defense against intravenous infection in immunocompetent animals, but lack of NK cells in T/B-cell deficient SCID mice led to increased susceptibility to infection (80).…”