MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity.
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.
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
Netanya S
NS
Utay
Human Immunology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Annelys
A
Roque
Human Immunology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
J Katherina
JK
Timmer
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
David R
DR
Morcock
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Claire
C
DeLeage
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
Anoma
A
Somasunderam
Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, United States of America.|Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
Amy C
AC
Weintrob
Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
Brian K
BK
Agan
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Jacob D
JD
Estes
Infectious Disease Clinical Research Program (IDCRP), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, United States of America.|Infectious Disease Clinic, Naval Medical Center San Diego, San Diego, California, United States of America.
Nancy F
NF
Crum-Cianflone
Human Immunology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Daniel C
DC
Douek
D060085:Coinfection / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007150:Immunohistochemistry; D055624:Methicillin-Resistant Staphylococcus aureus; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*