MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity

Netanya S. Utay, Annelys Roque, J. Katherina Timmer, David R. Morcock, Claire DeLeage, Anoma Somasunderam, Amy C. Weintrob, Brian K. Agan, Jacob D. Estes, Nancy F. Crum-Cianflone, Daniel C. Douek

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

People with HIV infection are at increased risk for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs). Lower CD4 T-cell counts, higher peak HIV RNA levels and epidemiological factors may be associated with increased risk but no specific immune defect has been identified. We aimed to determine the immunologic perturbations that predispose HIV-infected people to MRSA SSTIs. Participants with or without HIV infection and with MRSA SSTI, MRSA colonization or negative for MRSA were enrolled. Peripheral blood and skin biopsies from study participants were collected. Flow cytometry, flow cytometry with microscopy, multiplex assays of cell culture supernatants and immunohistochemistry were used to evaluate the nature of the immune defect predisposing HIV-infected people to MRSA infections. We found deficient MRSA-specific IFNγ+CD4 T-cell responses in HIV-infected people with MRSA SSTIs compared to MRSA-colonized participants and HIV-uninfected participants with MRSA SSTIs. These IFNγ+CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs. However, IFNγ responses to cytomegalovirus and Mycobacterium avium antigens and MRSA-specific IL-17 responses by CD4 T cells were intact. Upon stimulation with MRSA, peripheral blood mononuclear cells from HIV-infected participants produced less IL-12 and IL-15, key drivers of IFNγ production. There were no defects in CD8 T-cell responses, monocyte responses, opsonization, or phagocytosis of Staphylococcus aureus. Accumulation of CD3 T cells, CD4 T cells, IL-17+cells, myeloperoxidase+neutrophils and macrophage/myeloid cells to the skin lesions were similar between HIV-infected and HIV-uninfected participants based on immunohistochemistry. Together, these results indicate that MRSA-specific IFNγ+CD4 T-cell responses are essential for the control of initial and recurrent MRSA infections in HIV-infected people.

Original languageEnglish (US)
Article numbere1005580
JournalPLoS Pathogens
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2016

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Methicillin-Resistant Staphylococcus aureus
HIV Infections
Immunity
Soft Tissue Infections
HIV
Skin
T-Lymphocytes
Interleukin-17
Flow Cytometry
Immunohistochemistry
Mycobacterium avium
Interleukin-15
Myeloid Cells
Interleukin-12
CD4 Lymphocyte Count
Cytomegalovirus
Phagocytosis
Peroxidase
Staphylococcus aureus
Monocytes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Utay, N. S., Roque, A., Timmer, J. K., Morcock, D. R., DeLeage, C., Somasunderam, A., ... Douek, D. C. (2016). MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity. PLoS Pathogens, 12(4), [e1005580]. https://doi.org/10.1371/journal.ppat.1005580

MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity. / Utay, Netanya S.; Roque, Annelys; Timmer, J. Katherina; Morcock, David R.; DeLeage, Claire; Somasunderam, Anoma; Weintrob, Amy C.; Agan, Brian K.; Estes, Jacob D.; Crum-Cianflone, Nancy F.; Douek, Daniel C.

In: PLoS Pathogens, Vol. 12, No. 4, e1005580, 01.04.2016.

Research output: Contribution to journalArticle

Utay, NS, Roque, A, Timmer, JK, Morcock, DR, DeLeage, C, Somasunderam, A, Weintrob, AC, Agan, BK, Estes, JD, Crum-Cianflone, NF & Douek, DC 2016, 'MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity', PLoS Pathogens, vol. 12, no. 4, e1005580. https://doi.org/10.1371/journal.ppat.1005580
Utay NS, Roque A, Timmer JK, Morcock DR, DeLeage C, Somasunderam A et al. MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity. PLoS Pathogens. 2016 Apr 1;12(4). e1005580. https://doi.org/10.1371/journal.ppat.1005580
Utay, Netanya S. ; Roque, Annelys ; Timmer, J. Katherina ; Morcock, David R. ; DeLeage, Claire ; Somasunderam, Anoma ; Weintrob, Amy C. ; Agan, Brian K. ; Estes, Jacob D. ; Crum-Cianflone, Nancy F. ; Douek, Daniel C. / MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity. In: PLoS Pathogens. 2016 ; Vol. 12, No. 4.
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