Manipulation of Host Signaling by Vector-Borne and Non-Vector-Borne Pathogens

Infectious diseases affect individuals all over the world. Both vector-borne and non-vector pathogens that cause these illnesses have developed strategies to subvert immune recognition. Since the innate immune system is the first line of defense against potentially noxious substances, the host is also able to adjust innate immune signaling in order to perpetuate its survival. This host-pathogen interaction is highly conserved, ranging from plants to mammals. Unfortunately, there remains quite a disparity between the plethora of pathogens and what is known about host signaling in response to their recognition. Deciphering the modes by which vector-borne and non-vector-borne pathogens influence host signaling will ultimately provide a clearer understanding of targets for protective measures against these life-threatening diseases. The nod-like receptors (NLRs) are crucial components for host protection from a wide array of pathogen and danger associated molecular patterns. Whether they act alone or as a protein platform, NLRs effectively initiate key innate immune signaling cascades in order to promote the expression and/or secretion of pro-inflammatory genes and cytokines. Additionally, the inflammasome, a protein scaffold formed by NLRs/AIM2, the ASC adaptor molecule, and caspase-1 can elicit a potent form of cell death triggered by inflammation called pyroptosis. As a result, NLRs are very attractive to both the host and the pathogen: (1) for the host, it provides a method by which it can protect itself from intracellular detection of pathogens, while (2) for the pathogen, it is a target for manipulation so that it may propagate. This dissertation will provide an overview and insight regarding vector-borne and non-vector-borne pathogens and their effects on NLR signaling pathways.