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Publications of the Week

Systemic and Mucosal Mobilization of Granulocyte Subsets during Lentiviral Infection

By June 21, 2021June 24th, 2021No Comments

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This week we profile a recent publication in Immunology from Rhianna Jones (pictured, left) and Dr. Cordelia Manickham
(right) in Dr. Keith Reeve’s (center) lab at Harvard Medical School and the Beth Israel Deaconess Medical Center.
Dr. Reeves’ lab has recently begun the process of moving to Duke University.

Can you provide a brief overview of your lab’s current research focus?

The Reeves laboratories are focused on understanding the role of innate immune cells in modulating viral infections and other diseases in both humans and using nonhuman primate models. Our research over the past ten years has revealed significant heterogeneity among natural killer (NK) cells in tissues outside of peripheral blood and we were the first to characterize IL-17/IL-22-producing type 3 innate lymphoid cells (ILCs), memory NK cells, gamma chain deficient memory-like NK cells and NK-like B cells in nonhuman primates. More recent work has turned to Fc-mediated effector functions on a variety of cells types including recent studies on mucosal granulocytes. The highlighted recent publication in Immunology delineates granulocytes in chronic SHIV (simian-human immunodeficiency virus) infected macaques and was spearheaded by Cordelia Manickam, Ph.D., D.V.M. and Rhianna Jones in my laboratories.

What is the significance of the findings in this publication?

Granulocytes are innate immune cells and they generally include neutrophils, eosinophils and basophils. They are among the first lines of defense against pathogens both in peripheral and mucosal tissues through their capacity to release cytokines and neutrophil extracellular traps (NETs), as well as perform phagocytosis. However, their roles in mucosal tissues such as gut and reproductive tract have been underexplored. Since human mucosal tissue samples are often difficult to obtain, we comprehensively analyzed the granulocyte compartment in a wide range of mucosal and lymphoid tissues including colon, jejunum, cervix, vagina, liver, spleen, and lymph nodes of lentivirus-infected and experimentally naive rhesus macaques. We confirmed the profiles of each population in blood and tissues of rhesus macaques using a combination of imaging cytometry and flow cytometry.  Our findings provide a comprehensive landscape of the distribution of these cells and further showed that neutrophils and eosinophils were elevated in colon tissue, a primary site of HIV and SIV replication.

What are the next steps for this research?

While our data provides evidence that immune modulation by SIV occurs at the mucosal site of virus replication, it is not clear if these cells actually contribute to immune protection or tissue damage. Since HIV also causes systemic immune cell dysfunctions and destroys the protective gut barrier, we want to ascertain if the functions of infiltrating neutrophils and eosinophils in the colon are protective or pathogenic. Further, our current data provides only homeostatic and chronic disease snapshots of mucosal granulocytes. Therefore, our future studies will include longitudinal timepoints post infection in order to understand the timing and duration of granulocyte infiltration in gut tissues, any correlations with viral clearance and/or tissue pathology and associated modulations of microbiome.

This research was funded by:

NIH grants R01 DE026327, P01 AI120756, as well as the Harvard University Center for AIDS Research Advanced Laboratory Technologies Core (P30 AI060354)

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