BACKGROUND: The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive. METHODS AND RESULTS: We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-γKO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN-γ-dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN-γ and iNKT cells. CONCLUSIONS: Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN-γ produced, in part, by iNKT cells.
BACKGROUND: The commensal yeastCandida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicansinfection remain elusive. METHODS AND RESULTS: We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicansinfection was not observed in interferon-gamma knockout (IFN-γKO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN-γ-dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN-γ and iNKT cells. CONCLUSIONS: Our results indicate that coinfecting commensal bacteria exacerbate C. albicansinfection through IFN-γ produced, in part, by iNKT cells.
Authors: G Gonzalez-Aseguinolaza; C de Oliveira; M Tomaska; S Hong; O Bruna-Romero; T Nakayama; M Taniguchi; A Bendelac; L Van Kaer; Y Koezuka; M Tsuji Journal: Proc Natl Acad Sci U S A Date: 2000-07-18 Impact factor: 11.205
Authors: Alexander M de Bruin; Sten F Libregts; Marijke Valkhof; Louis Boon; Ivo P Touw; Martijn A Nolte Journal: Blood Date: 2011-11-23 Impact factor: 22.113
Authors: Edward E S Nieuwenhuis; Tetsuya Matsumoto; Mark Exley; Robbert A Schleipman; Jonathan Glickman; Dan T Bailey; Nadia Corazza; Sean P Colgan; Andrew B Onderdonk; Richard S Blumberg Journal: Nat Med Date: 2002-06 Impact factor: 53.440
Authors: Carlo Selmi; David L Balkwill; Pietro Invernizzi; Aftab A Ansari; Ross L Coppel; Mauro Podda; Patrick S Leung; Thomas P Kenny; Judy Van De Water; Michael H Nantz; Mark J Kurth; M Eric Gershwin Journal: Hepatology Date: 2003-11 Impact factor: 17.425
Authors: Emma C Reilly; Elizabeth A Thompson; Sandrine Aspeslagh; Jack R Wands; Dirk Elewaut; Laurent Brossay Journal: PLoS One Date: 2012-05-23 Impact factor: 3.240