AUTHOR=Nadella Vinod , Sharma Lalita , Kumar Pankaj , Gupta Pushpa , Gupta Umesh D. , Tripathi Srikant , Pothani Suresh , Qadri S. S. Y. H. , Prakash Hridayesh TITLE=Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03085 DOI=10.3389/fimmu.2019.03085 ISSN=1664-3224 ABSTRACT=

Sphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P against pathogenic Mycobacterium tuberculosis (H37Rv) in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization toward M1 phenotype, and secretion of interferon (IFN)-γ during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptor-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signaling components of inflammatory signaling pathways during M. tuberculosis infection, thus highlighting antimycobacterial potential of S-1P in animals. Our data suggest that enhancing S-1P levels by sphingolipid mimetic compounds/drugs can be used as an immunoadjuvant for boosting immunity against pathogenic mycobacteria.