NKT cells are responsible for the clearance of murine norovirus through the virus-specific secretory IgA pathway

• Published in: Biochemistry and biophysics reports 2020-03, Vol.21, p.100722-100722, Article 100722
• Main Authors: Ishikawa, Hiroki, Ino, Satoshi, Yamochi, Toshiko, Sasaki, Hiraku, Kobayashi, Takahiro, Kohda, Chikara, Takimoto, Masafumi, Tanaka, Kazuo
• Format: Article
• Language: English
• Subjects: Delayed growth; Murine norovirus-S7; NKT cells; Secretory IgA
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2019.100722

Norovirus infection cause epidemic nonbacterial gastroenteritis in patients. The immune mechanisms responsible for the clearance of virus are not completely understood. We examined whether NKT cells are effective against norovirus infection using CD1d KO mice. The body weights of 4-weeks-old CD1d KO mice that were infected with murine norovirus-S7 (MNV-S7) were significantly lower than those of non-infected CD1d KO mice. On the other hand, the body weights of infected WT mice were comparable to those of non-infected WT mice. Correspondingly, CD1d KO mice had an almost 1000-fold higher MNV-S7 burden in the intestine after infection in comparison to WT mice. The mechanism responsible for the insufficient MNV-S7 clearance in CD1d KO mice was attributed to reduced IFN-γ production early during MNV-S7 infection. In addition, the markedly impaired IL-4 production in CD1d KO mice resulted in an impaired MNV-S7-specific secretory IgA production after MNV-S7 infection which is associated with mucosal immunity. Thus, the present results provide evidence that NKT cells play an essential role in MNV-S7 clearance. •This is the first report that NKT cell is responsible for protection against MNV infection.•The growth curves of infected CD1d KO mice were significantly lower than non-infected CD1d KO mice.•MNV titers in fecal of CD1d KO mice were almost 1000-fold more than that of WT mice after infection.•MNV-specific sIgA production in CD1d KO mice was significantly lower resulting in insufficient MNV clearance.