TY - JOUR
T1 - Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells
AU - Tarumoto, Norihito
AU - Kinjo, Yuki
AU - Kitano, Naoki
AU - Sasai, Daisuke
AU - Ueno, Keigo
AU - Okawara, Akiko
AU - Izawa, Yuina
AU - Shinozaki, Minoru
AU - Watarai, Hiroshi
AU - Taniguchi, Masaru
AU - Takeyama, Haruko
AU - Maesaki, Shigefumi
AU - Shibuya, Kazutoshi
AU - Miyazaki, Yoshitsugu
N1 - Funding Information:
Financial support. This work was supported by grants from the Ministry of Health, Labor and Welfare of Japan (H23-shinkou-ippan-018 and H22-shinkou-ippan-008 to Y. M. and K. S., H23-shinkou-ippan-007 and H24-shinkou-ippan-013 to Y. M.); the Japan Society for the Promotion of Science and the Japanese Ministry of Education, Culture, Sports, Science and Technology (Y. K.); and the Takeda Science Foundation (Y. K.).
Funding Information:
Potential conflicts of interest. Y. K. reports receiving grant support from Takeda Science Foundation. Y. M. reports receiving grant support from Pfizer Inc., Astellas Pharma Inc., MSD, and Dainippon Sumitomo Pharma Co. Ltd. for other projects. K. S. reports receiving grant support from Pfizer Inc. and Dainippon Sumitomo Pharma Co. Ltd. for other projects. S. M. reports receiving grant support from Pfizer Inc., Astellas Pharma Inc., and Dainippon Sumitomo Pharma Co. Ltd. for other projects. All other authors report no potential conflicts.
PY - 2014/3
Y1 - 2014/3
N2 - 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-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--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- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.
AB - 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-KO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN--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- and iNKT cells.Conclusions. Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN- produced, in part, by iNKT cells.
KW - Candida albicans
KW - commensal bacteria
KW - glycolipid
KW - iNKT cell
KW - nonfermentative gram-negative bacteria
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U2 - 10.1093/infdis/jit534
DO - 10.1093/infdis/jit534
M3 - Article
C2 - 24096333
AN - SCOPUS:84894249542
VL - 209
SP - 799
EP - 810
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 5
ER -