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

Utay NS, Roque A, Timmer JK, Morcock DR, DeLeage C, Somasunderam A, Weintrob AC, Agan BK, Estes JD, Crum-Cianflone NF, Douek DC - PLoS Pathog. (2016)

Bottom Line: 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.These IFNγ+ CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.

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.

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Related in: MedlinePlus

Cytokine concentrations released into supernatant.Supernatant concentrations of IFNγ (A) and drivers of IFNγ production, IL-12 (B) and IL-15 (C), after MRSA stimulation of PBMCs were assayed using the Luminex platform. P-values were calculated using the Mann-Whitney U test.
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ppat.1005580.g002: Cytokine concentrations released into supernatant.Supernatant concentrations of IFNγ (A) and drivers of IFNγ production, IL-12 (B) and IL-15 (C), after MRSA stimulation of PBMCs were assayed using the Luminex platform. P-values were calculated using the Mann-Whitney U test.

Mentions: To evaluate comprehensively the responsiveness of MRSA-specific PBMCs, we measured cytokines released into the supernatant after stimulation with heat-killed MRSA. Indeed, PBMCs from HIV-infected participants with MRSA SSTIs produced less IFNγ and IL-12p70 than PBMCs from HIV-infected, MRSA-colonized participants (250 vs. 844 pg/ml, P = 0.01, Fig 2A; 8.7 vs. 31.8 pg/ml, P = 0.009, Fig 2B). IL-15 production was also significantly lower in HIV-infected MRSA SSTI participants compared to HIV-infected MRSA-negative (1.59 vs. 2.20 pg/ml, P = 0.02) and HIV-uninfected MRSA SSTI groups (1.59 vs. 3.37 pg/ml, P = 0.02; Fig 2C). Production of IL-17 and IL-10 did not differ significantly among groups, nor did IFNγ or IL-12p70 production in response to stimulation with CMV or C. albicans antigens. In sum, HIV-infected participants with MRSA SSTIs had decreased MRSA-specific IFNγ, IL-12p70 and IL-15 production.


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

Utay NS, Roque A, Timmer JK, Morcock DR, DeLeage C, Somasunderam A, Weintrob AC, Agan BK, Estes JD, Crum-Cianflone NF, Douek DC - PLoS Pathog. (2016)

Cytokine concentrations released into supernatant.Supernatant concentrations of IFNγ (A) and drivers of IFNγ production, IL-12 (B) and IL-15 (C), after MRSA stimulation of PBMCs were assayed using the Luminex platform. P-values were calculated using the Mann-Whitney U test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836670&req=5

ppat.1005580.g002: Cytokine concentrations released into supernatant.Supernatant concentrations of IFNγ (A) and drivers of IFNγ production, IL-12 (B) and IL-15 (C), after MRSA stimulation of PBMCs were assayed using the Luminex platform. P-values were calculated using the Mann-Whitney U test.
Mentions: To evaluate comprehensively the responsiveness of MRSA-specific PBMCs, we measured cytokines released into the supernatant after stimulation with heat-killed MRSA. Indeed, PBMCs from HIV-infected participants with MRSA SSTIs produced less IFNγ and IL-12p70 than PBMCs from HIV-infected, MRSA-colonized participants (250 vs. 844 pg/ml, P = 0.01, Fig 2A; 8.7 vs. 31.8 pg/ml, P = 0.009, Fig 2B). IL-15 production was also significantly lower in HIV-infected MRSA SSTI participants compared to HIV-infected MRSA-negative (1.59 vs. 2.20 pg/ml, P = 0.02) and HIV-uninfected MRSA SSTI groups (1.59 vs. 3.37 pg/ml, P = 0.02; Fig 2C). Production of IL-17 and IL-10 did not differ significantly among groups, nor did IFNγ or IL-12p70 production in response to stimulation with CMV or C. albicans antigens. In sum, HIV-infected participants with MRSA SSTIs had decreased MRSA-specific IFNγ, IL-12p70 and IL-15 production.

Bottom Line: 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.These IFNγ+ CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus