Monocyte Chemoattractant Protein-1-Dependent Increase of Vα14 NKT Cells in Lungs and Their Roles in Th1 Response and Host Defense in Cryptococcal Infection

Abstract

To elucidate the role of NKT cells in the host defense to cryptococcal infection, we examined the proportion of these cells, identified by the expression of CD3 and NK1.1, in lungs after intratracheal infection with Cryptococcus neoformans. This population increased on day 3 after infection, reached a peak level on days 6–7, and decreased thereafter. In Vα14 NKT cell-deficient mice, such increase was significantly attenuated. The proportion of Vα14 NKT cells, detected by binding to α-galactosylceramide-loaded CD1d tetramer, and the expression of Vα14 mRNA increased after infection with a similar kinetics. The delayed-type hypersensitivity response and differentiation of the fungus-specific Th1 cells was reduced in Vα14 NKT cell-deficient mice, compared with control mice. Additionally, elimination of this fungal pathogen from lungs was significantly delayed in Vα14 NKT cell-deficient mice. Production of monocyte chemoattractant protein (MCP)-1 in lungs, detected at both mRNA and protein levels, increased on day 1, reached a peak level on day 3, and decreased thereafter, which preceded the increase in NKT cells. Finally, the increase of total and Vα14+ subset of NKT cells after infection was significantly reduced in MCP-1-deficient mice. Our results demonstrated that NKT cells, especially Vα14+ subset, accumulated in a MCP-1-dependent manner in the lungs after infection with C. neoformans and played an important role in the development of Th1 response and host resistance to this fungal pathogen.

Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules

“…Many CD1d-restricted T cells coexpress CD161, which is expressed mostly on natural killer cells, and are referred to as natural killer T (NKT) cells (6). NKT cells rapidly secrete an array of cytokines after activation, and, although they constitute Ͻ1% of total T cells, they exert a critical influence in a variety of situations, including cancer (7) and bacterial, viral, parasitic, and fungal infections (8)(9)(10) and autoimmune diseases (11).…”

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

“…Studies in mice have revealed that a-GalCer treatment promotes resistance against infections, tumours and autoimmunity [15][16][17][18][19][20][21][22][23][24][25][26][27]. In a murine vaccination study, a-GalCer potentiated protective immune responses induced by malaria vaccines [28].…”

Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL‐4 and eotaxin production

“…NKT cell subpopulations may be double-negative, single-positive or double-positive with regards to CD4 and CD8 molecule expression [4,6,[7][8][9]. Recently, the involvement of NKT cells in modulating immune responses to various antigens has been implicated [7,[10][11][12][13][14][15][16][17][18][19]. They have been found to be essential in tumor rejection as well as in the prevention of autoimmune diseases, such as multiple sclerosis and chronic inflammatory demyelinating polyneuropathy [12][13][14].…”

“…Interestingly, NKT cells are reported to be involved in the promotion of both Th1-like reactions in response to intracellular pathogens [15] as well as the production of Th2 cytokines [16][17][18][19].…”