Systemic and mucosal mobilization of granulocyte subsets during lentiviral infection.

Journal Article (Journal Article)

Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver and whole blood from experimentally naïve and chronically SHIVsf162p3-infected RM were analysed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils-CD45+  CD66+  CD49d+ ; neutrophils-CD45+  CD66+  CD14+ ; and basophils-CD45+  CD123+  FcRε+ . Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged from 25·4% to 81·5% neutrophils, 0·59% to 13·3% eosinophils and 0·059% to 1·8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils and colorectal eosinophils were all observed in chronic lentiviral disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils and vaginal eosinophils of SHIVsf162p3-infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentiviral infection, most notably in the gastrointestinal mucosae where a significant inflammation and disruption occurs in lentivirus-induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention.

Full Text

Duke Authors

Cited Authors

  • Jones, R; Manickam, C; Ram, DR; Kroll, K; Hueber, B; Woolley, G; Shah, SV; Smith, S; Varner, V; Reeves, RK

Published Date

  • October 2021

Published In

Volume / Issue

  • 164 / 2

Start / End Page

  • 348 - 357

PubMed ID

  • 34037988

Pubmed Central ID

  • PMC8442246

Electronic International Standard Serial Number (EISSN)

  • 1365-2567

Digital Object Identifier (DOI)

  • 10.1111/imm.13376

Language

  • eng

Conference Location

  • England