The protective roles of NLRs during infection and tumor progression

The immune system has evolved to fight off numerous pathogens. The first line of defense against these pathogens are innate immune cells. Innate immune cells ingest pathogens and a family of cytosolic proteins, NOD-like receptors (NLR) and AIM2-like receptors (ALRs), recognize conserved sequences on pathogens. Recognition of pathogens by NLRs and ALRs alerts the immune system to the presence of an invader and subsequent control of infection. NLRs and ALRs also recognize endogenous cell danger signals that are released during cell stress.

Pathogens and tumor cells are capable of growing in a host with limited detection by the immune system. This evasion leads to a suboptimal immune response to both the bacteria and cancer cells resulting in enhanced infection and tumor growth. We investigated how the bacteria Francisella tularensis escapes recognition by the AIM2 receptor. We identified a novel gene important in bacterial folate metabolism that helps the bacteria escape immune recognition. The identification of this gene will help in the development of treatments for F. tularensis infection.

In addition, we investigated the role of the NLRC4 receptor in a mouse model of melanoma. We found that mice lacking NLRC4 developed significantly larger tumors and had a diminished immune response compared to mice that expressed NLRC4. We also observed decreased expression of NLRC4 in metastatic melanoma tissue in humans. Thus demonstrating that NLRC4 is important for initiating an immune response to melanoma and down regulating expression of NLRC4 is a way for the tumor to evade the immune response.