Adaptive reconfiguration of natural killer cells in HIV-1 infection
Human cytomegalovirus (HCMV) co-infection is highly prevalent within HIV-1 cohorts and is an important co-factor in driving ongoing immune activation, even during effective antiretroviral treatment (ART). HCMV infection has recently been associated with expansion of adaptive-like Natural Killer (NK)...
| Main Authors: | , , , , , |
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| Format: | Journal article |
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Frontiers Media
2018
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| _version_ | 1797065766100533248 |
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| author | Peppa, D Pedroza-Pacheco, I Pellegrino, P Williams, I Maini, M Borrow, P |
| author_facet | Peppa, D Pedroza-Pacheco, I Pellegrino, P Williams, I Maini, M Borrow, P |
| author_sort | Peppa, D |
| collection | OXFORD |
| description | Human cytomegalovirus (HCMV) co-infection is highly prevalent within HIV-1 cohorts and is an important co-factor in driving ongoing immune activation, even during effective antiretroviral treatment (ART). HCMV infection has recently been associated with expansion of adaptive-like Natural Killer (NK) cells, which harbor epigenetic alterations that impact on their cellular function and phenotype. The influence of HCMV co-infection on the considerable heterogeneity among NK cells and their functional responses to different stimuli was assessed in a cohort of HIV-1 infected individuals sampled during different stages of infection, compared to healthy subjects stratified according to HCMV serostatus. Our data demonstrate a reshaping of the NK cell pool in HIV-1 infection of HCMV-seropositive individuals, with an accentuated peripheral transition of CD56dim NK cells towards a mature CD57+CD85j+NKG2C+NKG2A- phenotype. Lack of PLZF further distinguishes adaptive NK cells from other NK cells expressing CD57 or NKG2C. PLZF- NK cells from HIV-infected individuals had high expression of CD2, were Siglec-7 negative and exhibited downregulation of key signaling molecules, SYK and FcεRI-γ, overwhelmingly displaying features of adaptive NK cells that correlate with HCMV serum Ab levels. Notably this adaptive-like signature was detected during early HIV-1 infection and persisted during treatment. Adaptive-like NK cell subsets in HIV-1-infected individuals displayed enhanced IFN-γ production following Fc-receptor triggering compared to their conventional NK cell counterparts, and their ability to produce TNF-α and degranulate was preserved. Together these data suggest that HMCV infection/reactivation, a hallmark of HIV-1 infection, plays a role in driving a relative expansion of NK cells with adaptive features during HIV-1 infection. The identification of selective NK subsets with retained effector activity in HIV-1-infected subjects raises the possibility of developing therapeutic strategies that exploit specific NK subpopulations to achieve better HIV-1 control. |
| first_indexed | 2024-03-06T21:33:16Z |
| format | Journal article |
| id | oxford-uuid:45632876-16fc-4cc8-98b5-78afc891a9d0 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:33:16Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:45632876-16fc-4cc8-98b5-78afc891a9d02022-03-26T15:07:33ZAdaptive reconfiguration of natural killer cells in HIV-1 infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:45632876-16fc-4cc8-98b5-78afc891a9d0Symplectic Elements at OxfordFrontiers Media2018Peppa, DPedroza-Pacheco, IPellegrino, PWilliams, IMaini, MBorrow, PHuman cytomegalovirus (HCMV) co-infection is highly prevalent within HIV-1 cohorts and is an important co-factor in driving ongoing immune activation, even during effective antiretroviral treatment (ART). HCMV infection has recently been associated with expansion of adaptive-like Natural Killer (NK) cells, which harbor epigenetic alterations that impact on their cellular function and phenotype. The influence of HCMV co-infection on the considerable heterogeneity among NK cells and their functional responses to different stimuli was assessed in a cohort of HIV-1 infected individuals sampled during different stages of infection, compared to healthy subjects stratified according to HCMV serostatus. Our data demonstrate a reshaping of the NK cell pool in HIV-1 infection of HCMV-seropositive individuals, with an accentuated peripheral transition of CD56dim NK cells towards a mature CD57+CD85j+NKG2C+NKG2A- phenotype. Lack of PLZF further distinguishes adaptive NK cells from other NK cells expressing CD57 or NKG2C. PLZF- NK cells from HIV-infected individuals had high expression of CD2, were Siglec-7 negative and exhibited downregulation of key signaling molecules, SYK and FcεRI-γ, overwhelmingly displaying features of adaptive NK cells that correlate with HCMV serum Ab levels. Notably this adaptive-like signature was detected during early HIV-1 infection and persisted during treatment. Adaptive-like NK cell subsets in HIV-1-infected individuals displayed enhanced IFN-γ production following Fc-receptor triggering compared to their conventional NK cell counterparts, and their ability to produce TNF-α and degranulate was preserved. Together these data suggest that HMCV infection/reactivation, a hallmark of HIV-1 infection, plays a role in driving a relative expansion of NK cells with adaptive features during HIV-1 infection. The identification of selective NK subsets with retained effector activity in HIV-1-infected subjects raises the possibility of developing therapeutic strategies that exploit specific NK subpopulations to achieve better HIV-1 control. |
| spellingShingle | Peppa, D Pedroza-Pacheco, I Pellegrino, P Williams, I Maini, M Borrow, P Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title | Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title_full | Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title_fullStr | Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title_full_unstemmed | Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title_short | Adaptive reconfiguration of natural killer cells in HIV-1 infection |
| title_sort | adaptive reconfiguration of natural killer cells in hiv 1 infection |
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