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 Gupta, Srikant Tripathi, Suresh Pothani, S.S.Y.H. Qadri, Hridayesh Prakash
Abstract
Sphingosine-1 phosphate (S-1P) is a key sphingolipid and involved in 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) also in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization towards M1 phenotype and secretion of IFN- during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptors-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signalling components of inflammatory signalling pathways during M. tb infection thus highlighting anti-mycobacterial potential of S-1P in animals. Taken together, our data suggests that boosting S-1P levels by Sphingolipids mimetic compounds / drugs can be used as immune adjuvant for boosting immunity against pathogenic mycobacteria.