TY - JOUR
T1 - Dectin-2-dependent host defense in mice infected with serotype 3 Streptococcus pneumoniae
AU - Akahori, Yukiko
AU - Miyasaka, Tomomitsu
AU - Toyama, Masahiko
AU - Matsumoto, Ikumi
AU - Miyahara, Anna
AU - Zong, Tong
AU - Ishii, Keiko
AU - Kinjo, Yuki
AU - Miyazaki, Yoshitsugu
AU - Saijo, Shinobu
AU - Iwakura, Yoichiro
AU - Kawakami, Kazuyoshi
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Health, Labour and Welfare of Japan (H22-SHINKOU-IPPAN-014 to KK and H25-SHINKOU-WAKATE-005 to YK), a grant from the Japan Agency for Medical Research and Development, AMED (the Research Program on Emerging and Re-emerging Infectious Diseases), aid funding from the Takeda Science Foundation to YK, and Joint Usage/Research Program of Medical Mycology Research Center, Chiba University [15–19] to KK.
Publisher Copyright:
© 2015 Akahori et al.
PY - 2016/1/5
Y1 - 2016/1/5
N2 - Background: Streptococcus pneumoniae, a major causative bacterial pathogen of community-acquired pneumonia, possesses a thick polysaccharide capsule. Host defense against this bacterium is mediated by activation of innate immune cells that sense bacterial components. Recently, C-type lectin receptors (CLRs) have garnered much attention in elucidating the recognition mechanism of pathogen-derived polysaccharides. Methods: In the present study, we first compared the clinical course and neutrophil accumulation in the lungs of Dectin-2 knock-out (KO) and wild type (WT) mice. Mice were infected intratracheally with a serotype 3 strain of S. pneumoniae, and S. pneumoniae bacterial engulfment by neutrophils and inflammatory cytokine and anti-pneumococcal polysaccharide-specific IgG levels were evaluated in bronchoalveolar lavage fluid (BALF). We also examined the effect of Dectin-2 deficiency on interleukin (IL)-12 production by bone marrow-derived dendritic cells (BM-DCs) stimulated with the bacterial components. Results: S. pneumonia-infected Dectin-2KO mice had a shorter survival time, larger bacterial burden and lower interferon gamma (IFN-γ) production in the lungs than WT mice. Although neutrophilic infiltration in the lungs was equivalent between Dectin-2KO mice and WT mice, S. pneumonia engulfment by neutrophils was attenuated in Dectin-2KO mice compared to WT mice. The anti-pneumococcal polysaccharide-specific IgG and IgG3 levels in BALF were lower in Dectin-2KO mice than in WT mice. When BM-DCs were stimulated with S. pneumoniae culture supernatant or its Concanavalin A (ConA)-bound fraction, IL-12 production was abrogated in Dectin-2KO mice compared to WT mice. Conclusions: We demonstrated that Dectin-2 is intimately involved in the host defense against infection with a serotype 3 strain of S. pneumoniae. Dectin-2-dependent IL-12 production may contribute to IFN-γ synthesis and subsequent production of serotype-specific anti-capsular polysaccharide IgG after S. pneumoniae infection, which may promote S. pneumoniae bacterial opsonization for engulfment.
AB - Background: Streptococcus pneumoniae, a major causative bacterial pathogen of community-acquired pneumonia, possesses a thick polysaccharide capsule. Host defense against this bacterium is mediated by activation of innate immune cells that sense bacterial components. Recently, C-type lectin receptors (CLRs) have garnered much attention in elucidating the recognition mechanism of pathogen-derived polysaccharides. Methods: In the present study, we first compared the clinical course and neutrophil accumulation in the lungs of Dectin-2 knock-out (KO) and wild type (WT) mice. Mice were infected intratracheally with a serotype 3 strain of S. pneumoniae, and S. pneumoniae bacterial engulfment by neutrophils and inflammatory cytokine and anti-pneumococcal polysaccharide-specific IgG levels were evaluated in bronchoalveolar lavage fluid (BALF). We also examined the effect of Dectin-2 deficiency on interleukin (IL)-12 production by bone marrow-derived dendritic cells (BM-DCs) stimulated with the bacterial components. Results: S. pneumonia-infected Dectin-2KO mice had a shorter survival time, larger bacterial burden and lower interferon gamma (IFN-γ) production in the lungs than WT mice. Although neutrophilic infiltration in the lungs was equivalent between Dectin-2KO mice and WT mice, S. pneumonia engulfment by neutrophils was attenuated in Dectin-2KO mice compared to WT mice. The anti-pneumococcal polysaccharide-specific IgG and IgG3 levels in BALF were lower in Dectin-2KO mice than in WT mice. When BM-DCs were stimulated with S. pneumoniae culture supernatant or its Concanavalin A (ConA)-bound fraction, IL-12 production was abrogated in Dectin-2KO mice compared to WT mice. Conclusions: We demonstrated that Dectin-2 is intimately involved in the host defense against infection with a serotype 3 strain of S. pneumoniae. Dectin-2-dependent IL-12 production may contribute to IFN-γ synthesis and subsequent production of serotype-specific anti-capsular polysaccharide IgG after S. pneumoniae infection, which may promote S. pneumoniae bacterial opsonization for engulfment.
KW - Anti-capsular polysaccharide IgG
KW - Dectin-2
KW - IFN-γ
KW - Neutrophils
KW - Streptococcus pneumonia
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UR - http://www.scopus.com/inward/citedby.url?scp=84959173836&partnerID=8YFLogxK
U2 - 10.1186/s12865-015-0139-3
DO - 10.1186/s12865-015-0139-3
M3 - Article
C2 - 26727976
AN - SCOPUS:84959173836
VL - 17
JO - BMC Immunology
JF - BMC Immunology
SN - 1471-2172
IS - 1
M1 - 1
ER -