The present study was designed to elucidate the role of V § 14 + NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using J § 281 gene-disrupted mice (J § 281KO mice) that lacked this lymphocyte subset. In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild-type (WT) mice. The proportion of V § 14 + NKT cells, detected by an § -galactosylceramide ( § -GalCer)-loaded CD1d tetramer, increased in the lung after S. pneumoniae infection. This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)-1, which was produced in the early phase of infection in WT mice. In the lungs of J § 281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice. In support of this finding, macrophage inflammatory protein (MIP)-2 and TNF- § synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in J § 281KO mice, compared to WT mice. In addition, treatment of mice with § -GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of V § 14 + NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.
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.
Osteopontin (OPN, also known as Eta-1), a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in granulomatous lesions caused by Mycobacterium tuberculosis infection. In the present study, we compared plasma concentrations of OPN in patients with active pulmonary tuberculosis with those of healthy control subjects and patients with sarcoidosis, another disease associated with granuloma formation. Plasma OPN levels were significantly higher in patients with tuberculosis (n = 48) than in control subjects (n = 34) and patients with sarcoidosis (n = 20). OPN levels correlated well with severity of pulmonary tuberculosis, as indicated by the size of lung lesions on chest X-ray films. Furthermore, chemotherapy resulted in a significant fall in plasma OPN levels. In patients with tuberculosis, plasma OPN concentrations correlated significantly with those of interleukin (IL)-12. In vitro experiments showed that OPN production by peripheral blood mononuclear cells infected with Mycobacterium bovis bacillus Calmette-Guérin preceded the synthesis of IL-12 and interferon-gamma and that the neutralizing anti-OPN monoclonal antibody significantly reduced the production of IL-12 and interferon-gamma. Our results suggest that OPN may be involved in the pathologic process associated with active pulmonary tuberculosis by inducing IL-12-mediated type 1 T helper cell responses.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.