HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli

Stephanie M. Dillon, Jennifer Manuzak, Amanda K. Leone, Eric J. Lee, Lisa M. Rogers, Martin D. McCarter, Cara C. Wilson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive Th1 and Th17 cells in normal human intestinal lamina propria (LP). In this article, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMCs), commensal E. coli, and CCR5-tropic HIV-1 Bal. Addition of heat-killed E. coli to HIV-1-exposed LPMCs resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1-exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, on MHC class II-restricted Ag presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.

Original languageEnglish (US)
Pages (from-to)885-896
Number of pages12
JournalJournal of Immunology
Volume189
Issue number2
DOIs
StatePublished - Jul 15 2012
Externally publishedYes

Fingerprint

HIV Infections
HIV-1
Mucous Membrane
Th17 Cells
Escherichia coli
T-Lymphocytes
Th1 Cells
Infection
Interleukin-17
In Vitro Techniques
Dendritic Cells
Cell Culture Techniques
Hot Temperature
HIV
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli. / Dillon, Stephanie M.; Manuzak, Jennifer; Leone, Amanda K.; Lee, Eric J.; Rogers, Lisa M.; McCarter, Martin D.; Wilson, Cara C.

In: Journal of Immunology, Vol. 189, No. 2, 15.07.2012, p. 885-896.

Research output: Contribution to journalArticle

Dillon, Stephanie M. ; Manuzak, Jennifer ; Leone, Amanda K. ; Lee, Eric J. ; Rogers, Lisa M. ; McCarter, Martin D. ; Wilson, Cara C. / HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli. In: Journal of Immunology. 2012 ; Vol. 189, No. 2. pp. 885-896.
@article{b4bae6b5cc7640c08f0c59f816ddee37,
title = "HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli",
abstract = "Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive Th1 and Th17 cells in normal human intestinal lamina propria (LP). In this article, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMCs), commensal E. coli, and CCR5-tropic HIV-1 Bal. Addition of heat-killed E. coli to HIV-1-exposed LPMCs resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1-exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, on MHC class II-restricted Ag presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.",
author = "Dillon, {Stephanie M.} and Jennifer Manuzak and Leone, {Amanda K.} and Lee, {Eric J.} and Rogers, {Lisa M.} and McCarter, {Martin D.} and Wilson, {Cara C.}",
year = "2012",
month = "7",
day = "15",
doi = "10.4049/jimmunol.1200681",
language = "English (US)",
volume = "189",
pages = "885--896",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli

AU - Dillon, Stephanie M.

AU - Manuzak, Jennifer

AU - Leone, Amanda K.

AU - Lee, Eric J.

AU - Rogers, Lisa M.

AU - McCarter, Martin D.

AU - Wilson, Cara C.

PY - 2012/7/15

Y1 - 2012/7/15

N2 - Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive Th1 and Th17 cells in normal human intestinal lamina propria (LP). In this article, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMCs), commensal E. coli, and CCR5-tropic HIV-1 Bal. Addition of heat-killed E. coli to HIV-1-exposed LPMCs resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1-exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, on MHC class II-restricted Ag presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.

AB - Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive Th1 and Th17 cells in normal human intestinal lamina propria (LP). In this article, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMCs), commensal E. coli, and CCR5-tropic HIV-1 Bal. Addition of heat-killed E. coli to HIV-1-exposed LPMCs resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1-exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, on MHC class II-restricted Ag presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.

UR - http://www.scopus.com/inward/record.url?scp=84863621018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863621018&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1200681

DO - 10.4049/jimmunol.1200681

M3 - Article

VL - 189

SP - 885

EP - 896

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -