# MAPK signaling pathways in host immune regulation during Mycobacterium tuberculosis infection

## TL;DR

This paper reviews how MAPK signaling pathways regulate immune responses during tuberculosis infection and explores potential therapeutic strategies targeting these pathways.

## Contribution

The paper systematically summarizes the roles of p38, ERK, and JNK in TB immunity and discusses novel therapeutic strategies targeting MAPK signaling.

## Key findings

- MAPK signaling regulates inflammation, autophagy, apoptosis, and immune cell differentiation during TB.
- p38, ERK, and JNK pathways have distinct roles in anti-TB immunity within macrophages, neutrophils, and T cells.
- Targeting MAPK signaling offers a theoretical framework for developing new TB treatments.

## Abstract

Tuberculosis (TB) is one of the world’s leading causes of death from a single infectious agent, with Mycobacterium tuberculosis (Mtb) primarily infecting the lungs via the respiratory tract. Following infection, immune cells such as macrophages and neutrophils phagocytose Mtb and initiate complex inflammatory and immune responses, driving the formation of granulomas and cavities within the lungs, ultimately leading to structural damage. In this intricate cascade, the MAPK signaling emerges as a critical regulator, orchestrating various cellular processes including inflammatory signaling, autophagy, apoptosis, and immune cell differentiation. Emerging evidence indicates that MAPK signaling critically shapes anti-TB immunity predominantly within macrophages, neutrophils, T cells and dendritic cells. Through extensive crosstalk among immune cells, MAPK signaling influences both host defense and disease progression. This review systematically summarizes current advances in understanding MAPK-mediated immune regulation during TB infection, with particular emphasis on the distinct roles of p38, ERK, and JNK signaling pathways. Furthermore, we discuss emerging therapeutic strategies to enhance anti-mycobacterial immunity by targeting MAPK signaling, thereby providing a valuable theoretical framework for the development of novel TB treatments.