Frontiers in Immunology (Jan 2020)

Sphingosine-1-Phosphate (S-1P) Promotes Differentiation of Naive Macrophages and Enhances Protective Immunity Against Mycobacterium tuberculosis

  • Vinod Nadella,
  • Lalita Sharma,
  • Pankaj Kumar,
  • Pushpa Gupta,
  • Umesh D. Gupta,
  • Srikant Tripathi,
  • Suresh Pothani,
  • S. S. Y. H. Qadri,
  • Hridayesh Prakash

DOI
https://doi.org/10.3389/fimmu.2019.03085
Journal volume & issue
Vol. 10

Abstract

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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.

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