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

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

doi:10.3389/fimmu.2019.03085

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.

Highlights

Tuberculosis (TB) is a global disease and one of the major causes of mortality worldwide where an approximate one-third of the global population is infected with the causative agent Mycobacterium tuberculosis [1]
Our previous study had demonstrated that S-1P/Sphk-1– mediated antimycobacterial responses are independent of tumor necrosis factor (TNF)-α [17]; a component of immunity that is sufficient to eliminate a large number of intracellular pathogens
S-1P enhanced the secretion of these cytokines by naive macrophages, revealing its adjuvant-like potential. These results revealed the involvement of S-1P in augmenting pro-inflammatory immune responses in macrophages, which are paramount for controlling M. tuberculosis infection

Summary

Introduction

Tuberculosis (TB) is a global disease and one of the major causes of mortality worldwide where an approximate one-third of the global population is infected with the causative agent Mycobacterium tuberculosis [1].

Methods

Results

Conclusion