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Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection
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Clin. Vaccine Immunol
published online ahead of print on 3 September 2014
Dallas Brown & Joseph J. Mattapallil*
Uniformed Services University of the Health Sciences, Bethesda, MD 20814
ABSTRACT
The gastrointestinal tract (GIT) is a primary site for human immunodeficiency virus (HIV) infection, replication and dissemination. After an initial explosive phase of infection, HIV establishes latency. In addition to CD4 T cells, macrophages are readily infected which can persist for long periods of time. Though macrophages at various systemic sites are infected, those present in the GIT constitute a major cellular reservoir due to the abundance of these cells at these mucosal sites. Here we review some of the important findings regarding what is known about the macrophage reservoir in the gut and explore potential approaches being pursued in the field to reduce this reservoir. Developing strategies that can lead to a functional cure will need to incorporate approaches that can eradicate the macrophage reservoir in the GIT.
Given the abundance of the macrophage reservoir in the gut, functional cure strategies would need to target these cellular sources of infection for it to be effective. A number of novel strategies that target macrophages have been proposed and are in the early stages of development that may hold promise........
Conclusion
Gut macrophages constitute a major cellular reservoir of HIV infection. There is considerable debate as to how these gut macrophages get infected in the absence of key cellular receptors required for HIV infection, and whether or not HIV actively replicates in these cells once infected. It is difficult to determine at this point how easy it will be to eradiate the gut macrophage reservoir and numerous challenges remain.
Additional studies are needed to better clarify these issues. It is clear, however, that given their long life span, infected gut macrophages play a key role in HIV persistence. Developing strategies that can completely eradiate these cellular sources of infection are essential for obtaining a functional cure in HIV infected patients.
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