Despite the low TNF-α titre in the infected SphK-1++ macrophages, their increased resistance to infection was found to be due to the enhanced expression of LAMP-2, iNOs, p-p38 and the elevated S1P titre, which all together conferred optimum defenses in these macrophages against M. smegmatis in a TNF independent manner. This evidence concerns the gene SPHK1 and infection.