The innate immune response represents the body’s first line of defense against pathogens.

Cells of the innate immune system, including natural killer cells, monocytes, and dendritic cells, constantly survey the body for non-self antigens through a vast array of non-specific pattern recognition molecules. Upon activation, innate immune cells respond rapidly, without the need for prior antigen sensitization, and have been shown to play a central role in the early control of the foreign invader as well as in the induction of the ensuing adaptive immune response.

Increasing evidence suggests that the first events that occur between the virus and the host following HIV-1 infection determine the speed of disease progression, suggesting that the quality of the innate immune response may have a profound impact on the ability of the immune system to gain control over the infecting virus.

Different components of the innate immune system can impact HIV-1 pathogenesis. Persistent stimulation of immune cells via Toll-like receptors (TLR), either due to intestinal translocation of microbial TLR4 ligands during chronic infection or due to stimulation of TLR7/8 by HIV-1-encoded nucleotide repeats, can drive immune activation providing a fertile environment for the virus replication.

Epidemiologic and functional studies demonstrate that the combined expression of specific NK cell receptors along with their HLA class I ligands is associated with slower disease progression, suggesting that NK cells may place vital early control over HIV-1 replication.

Furthermore, HIV-1 can modulate dendritic cell functions, and an altered DC phenotype/maturation status has a dramatic impact on the quality of the adaptive immune response to the virus.

Investigators at the Ragon Institute are actively engaged in defining the innate immune pathways involved in HIV-1 pathogenesis, and are exploring ways to harness innate immunity to gain more effective control over HIV-1 replication.

Laboratories which focus on Innate Immunity:
		Altfeld Lab
		Alter Lab