Mycobacterium bovis BCG-induced protection against cutaneous and systemic Leishmania major infections of mice

Abstract

We examined the protective effects of Mycobacterium bovis bacillus Calmette-Guérin (BCG) administration on Leishmania major infections of BALB/c and P/J mice. There were two treatment protocols. In the first, the footpads of naive animals were inoculated with mixtures of L. major and BCG (viable or heat killed) or the soluble mycobacterial antigen, purified protein derivative. Viable BCG, but not heat-killed BCG or purified protein derivative, inoculated with L. major amastigotes into the footpads of naive BALB/c or P/J mice protected these animals from the metastatic spread of parasites to the viscera and from ensuing lethal systemic infection. This treatment also induced cures of the cutaneous lesions of P/J mice but not of BALB/c mice. In the second protocol, we induced an immune response to BCG before inoculation of L. major. BCG given intraperitoneally 10 days before infection of footpads with leishmania offered protection against the metastatic spread of amastigotes in both P/J and BALB/c mice, regardless of intralesional treatment, and modulated the severity of cutaneous infection by 30 to 50%. Inoculation of a mixture of viable BCG and L. major amastigotes into BCG-immune mice completely protected both BALB/c and P/J strains from cutaneous disease; we recovered no parasites from the inoculated footpads of these animals. Furthermore, each of the nonspecifically protected mice of both the BALB/c and P/J strains developed immunity to rechallenge with viable L. major. Injection of amastigotes at a site remote from the original lesion, the contralateral footpad, resulted in the complete clearance of parasites in the inoculum with no evidence of either cutaneous or systemic disease over an extended observation period.