Contribution of NKT cells to the immune response and pathogenesis 2 triggered by the infection with respiratory viruses

Abstract

The human respiratory syncytial virus (hRSV) and the human metapneumovirus 26 (hMPV) cause acute respiratory tract infections in children worldwide. Natural killer T 27 (NKT) cells are unconventional T lymphocytes, and their TCRs recognize glycolipids 28 bound to the MHC-I-like CD1d molecule. These cells modulate the inflammatory response 29 in viral infections. Here, we evaluated the contribution of NKT cells to both hRSV and 30 hMPV infections. A significant decrease of neutrophils and CD103+ DCs infiltration to the 31 lungs, as well as increased production of IFN-γ, were observed upon hRSV-infection in 32 CD1d-deficient BALB/c mice, as compared to wild-type control mice. However, this effect 33 was not observed in the CD1d-deficient BALB/c mice upon infection with hMPV. 34 Importantly, reduced expression of CD1d in CD103+ DCs and epithelial cells was found in 35 hRSV- but not in hMPV-infected mice. Besides, a reduction in the expression of CD1d in 36 alveolar macrophages of lungs from hRSV- and hMPV-infected mice was found. Such 37 reduction of CD1d expression interfered with the NKT activation, and consequently the IL- 38 2 secretion was reduced in vivo and in vitro in both hRSV and hMPV infections. 39 Furthermore, the increased NKT cells recruited to the lungs in response to hRSV-infection - 40 but not hMPV- exhibited a Th-1 like profile. In conclusion, the balance of the quantity and 41 quality of these NKT cells exerts different roles during the immunopathology-associated 42 with either hRSV or hMPV infection.