Bacterial Lysates Modulate Human Macrophage Responses by Inducing BPI Production and Autophagy

TL;DR

This study shows that bacterial lysates can boost human macrophage responses by increasing BPI production and autophagy, which may help fight tuberculosis.

Contribution

The study reveals that bacterial lysates modulate macrophage responses through BPI and autophagy, offering new insights for host-directed tuberculosis therapies.

Findings

Bacterial lysates induce diverse immunostimulatory effects in macrophages, including cytokine production and BPI expression.

BPI levels are elevated in TB patients and decrease with treatment, suggesting its potential as a biomarker.

Lysates reduce intracellular mycobacterial burden and induce autophagy in macrophages.

Abstract

Bacterial lysates have emerged as promising immunomodulatory agents that can enhance innate immune responses. Given the crucial role of macrophages in recognizing and controlling intracellular pathogens such as Mycobacterium tuberculosis, this study aimed to evaluate the immunological effects of selected bacterial lysates on human monocyte-derived macrophages (MDMs). We examined the ability of commercial bacterial lysates, Pulmonarom, Ismigen, Uro-Vaxom, and a lysate of M. tuberculosis H37 Ra (LMtb) to stimulate the production of key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-8. In addition, we investigated whether these lysates could modulate the expression of bactericidal/permeability-increasing protein (BPI), a critical antimicrobial effector, and assessed their ability to reduce the intracellular burden of mycobacteria and induce autophagy. The results demonstrate diverse immunostimulatory profiles among the lysates, highlighting differences in both inflammatory and antimicrobial responses that may be relevant for host-directed therapeutic strategies against tuberculosis. Notably, beyond the in vitro antimycobacterial activity observed for BPI, this protein was also found to be elevated in both serum and bronchoalveolar lavage fluid from patients with active TB, reflecting local and systemic immune activation. Furthermore, the reduction in BPI levels after treatment suggests its potential utility for following the dynamics of infection.

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