Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 799-810 |
| Number of pages | 12 |
| Journal | Journal of Infectious Diseases |
| Volume | 209 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2014 Mar |
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Keywords
- Candida albicans
- commensal bacteria
- glycolipid
- iNKT cell
- nonfermentative gram-negative bacteria
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
Cite this
Exacerbation of invasive candida albicans infection by commensal bacteria or a glycolipid through IFN- Produced in part by iNKT cells. / Tarumoto, Norihito; Kinjo, Yuki; Kitano, Naoki; Sasai, Daisuke; Ueno, Keigo; Okawara, Akiko; Izawa, Yuina; Shinozaki, Minoru; Watarai, Hiroshi; Taniguchi, Masaru; Takeyama, Haruko; Maesaki, Shigefumi; Shibuya, Kazutoshi; Miyazaki, Yoshitsugu.
In: Journal of Infectious Diseases, Vol. 209, No. 5, 03.2014, p. 799-810.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84894249542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894249542&partnerID=8YFLogxK
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 -