J Immunol. 2025 Nov 15:vkaf146. doi: 10.1093/jimmun/vkaf146. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that employs several strategies to evade the host immune system to establish a favorable niche inside the macrophages. One of the major immune evasion strategies involves induction of T helper 2 (Th2)-type response, which in turn downregulates host’s antimycobacterial Th1-type response. Approximately 10% of the Mtb genome is made up of the PE (proline-glutamine))/PPE (proline-proline-glutamine) family of proteins, whose functions are still not fully understood. PPE18, a member of this family was found to activate interleukin-10/Th2-type responses by interacting with TLR2 11 to 15 leucine-rich repeat domain. PPE18 was found to inhibit phagosomal acidification and major histocompatibility complex class II-mediated antigen presentation, allowing the bacterium to persist inside macrophages. Mice infected with ppe18 knockout strain of Mtb had lower bacterial burden and better survival rate. In this review, we highlight the functional importance of PPE18 in mycobacterial virulence and explore the potential of PPE18 as a target for therapeutic drug and vaccine development.

PMID:41240377 | DOI:10.1093/jimmun/vkaf146