# Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection

## TL;DR

This study shows that miR-126 in zebrafish helps protect against mycobacterial infection by regulating immune pathways involving Tsc1 and Cxcl12a.

## Contribution

The study identifies miR-126 as a protective factor in mycobacterial infection through Tsc1/mTOR and Cxcl12a/Ccr2 pathways in zebrafish.

## Key findings

- miR-126 knockdown increases susceptibility to mycobacterial infection in zebrafish.
- Tsc1a expression suppresses immune response and increases bacterial burden via mTOR inhibition.
- Cxcl12a/Ccr2 signaling affects macrophage recruitment and cell death around granulomas.

## Abstract

Knockdown of miR-126 increases susceptibility to mycobacterial infection which can be independently reversed by targeting Tsc1/mTOR or ccr2 implicating macrophage function.

Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish–Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.