Antimicrobial mechanisms in response to Mycobaterium leprae infection
- Author(s): Dang, Angeline Tilly
- Advisor(s): modlin, robert l
- et al.
The human body is constantly exposed to a myriad of bacterial organisms, and in
most cases, colonization of the host by these commensal bacteria is harmless and may even
be beneficial. However, a subset of bacteria are pathogenic causing debilitating health that
can lead to fatal diseases. Many microbes deploy strategies to evade and impair the host
response, further contributing to disease severity. In response to infectious agents, the host
can control and subvert infections by triggering both innate and adaptive immunity. The
microenvironment in which an infections occurs greatly dictates the strength, quality, and
duration of immune responses. Herein, we demonstrate mechanisms for triggering
protective immune responses during Mycobacterium leprae infection. Specifically, treatment
of M. leprae-infected CD1a+ Langerhans cells, a dendritic cells subset localized in the skin and mucosa, with IFN-g induces autophagy, leading to increased antimicrobial activity and
antigen presentation to T cells. Furthermore, T cells secrete elevated amounts of IFN-g
following antigenic activation, providing an amplification loop to further augment effective
host immunity. As M. leprae predominantly infect and reside in macrophages, we also
investigated mechanisms of macrophage activation. Our data reveals that treatment of M.
leprae-infected monocyte-derived-macrophages with IL-26, a T cell cytokine, results in
reduced viability of intracellular bacteria. IL-26 may have dual roles in antimycobacterial
defense, one which involves binding to bacterial bacilli and directly reducing its viability; and
the other involving activation of infected macrophages, increasing bacterial traffic to the
lysosomes, where they are degraded.