Innate Immunity

Our faculty, students, and fellows are engaged in several areas of research pertaining to the innate immune response. Central to innate defense against pathogenic microorganisms is the ability of innate immune cells such as macrophages to internalize particles by phagocytosis. Quantitative fluorometric and microscopic methods are being used to delineate the mechanisms and regulation of phagocytosis. Macrophages and dendritic cells of the innate immune response process antigens into structures that are capable of being recognized by T cells of the adaptive immune response.

We are currently investigating mechanisms involved in antigen uptake and presentation to T cells, along with studies of how pathogens interfere with these processes. We are also engaged in research pertaining to innate immune responses to specific bacterial, viral, and fungal pathogens. Recent research has revealed that macrophages can sense bacterial molecules within the cytosol, which triggers expression of various cytokines, and other pro-inflammatory genes. Ongoing research in our Department involves the identification of signaling molecules and transcriptional regulators that are specific to this cytosolic surveillance pathway, using the Gram-positive intracytosolic bacterium, Listeria monocytogenes as a model pathogen.

The effects of innate immunity on pathogenesis of Vaccinia virus is also being investigated. In particular, mechanisms through which interferons and toll-like receptor signaling pathways affect vaccinia viral replication and spread in the lung is being studied. The initiation of pulmonary immunity to fungal pathogens requires the phagocytic cells of the lung innate system, including alveolar macrophages, dendritic cells, and neutrophils. In response to fungal infection, these cells produce early inflammatory mediators, which play a central role in the development of adaptive immunity against fungi. Current research in our Department is focused on understanding the cellular and molecular effectors involved in the initiation of immunity to model fungal pathogens such as Cryptococcus neoformans.