Toll-like receptor 4 defective mice carrying point or null mutations do not show increased susceptibility toCandida albicansin a model of hematogenously disseminated infection

Abstract

We have studied the role of TLR4 in murine defenses against Candida albicans in two TLR4-defective mouse strains: C3H/HeJ mice which have defective TLR4 signaling, and TLR4-/- knockout mice. Both TLR4-defective mice strains experimentally infected with virulent C. albicans cells showed no significant difference in survival as compared with their respective controls. Recruitment of neutrophils to the peritoneal cavity of i.p. infected mice was not affected in TLR4-/-animals, but significantly enhanced in C3H/HeJ mice, compared with their control mice. In vitro production of TNF-alpha by macrophages from both types of TLR4-defective mice, in response to yeasts and hyphae of C. albicans, was not diminished as compared with production by macrophages from wild-type mice. In vitro production of TNF-alpha by yeast-stimulated splenocytes from mice intravenously infected with the low-virulence C. albicans PCA2 strain was not affected in TLR4-defective mice, but the TNF-alpha production in response to hyphae was higher in TLR4-defective than in control animals; the production of IFN-gamma by these splenocytes was similar to controls, as well as the frequency of IFN-gamma-producing CD4+T lymphocytes, indicating that TLR4-defective mice are capable of mounting a Th1 adaptive immune response. Our data indicate that TLR4 is dispensable for murine immune resistance to C. albicans.

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…TLR4-defective C3H/HeJ mice have been reported to be more susceptible to disseminated candidiasis. 183 Similar results were obtained in models of intragastric infection and intravenous re-infection. 182 However in intravenous infection models, TLR4-/-mice survived longer upon C. albicans hyphae infection, 182 while no difference was observed between the TLR4-/-and wild-type mice upon C. albicans yeasts infection.…”

Direct Toll-Like Receptor-Mediated Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Macrophages

“…Total spleen cells were obtained by collagenase D treatment of the organ as previously described [13,14]. Erythrocytes were lysed in ammonium chloride buffer.…”

Killed Candida albicans Yeasts and Hyphae Inhibit Gamma Interferon Release by Murine Natural Killer Cells

“…We have previously described that TLR2 is the major receptor that activates macrophages in response to C. albicans (19,29). Since we found that C. albicans cells inhibit IFN-␥ production by NK cells, we investigated whether TLR2 might be involved in this effect.…”

“…There is evidence indicating that signal transduction mediated by TLRs is essential for murine resistance to disseminated C. albicans infection, basically through the induction of cytokine and chemokine release (4,11,16,(19)(20)(21)(28)(29)(30).…”