Increased IFN-γ production by NK and CD3+/CD56+ cells in sexually HIV-1-exposed but uninfected individuals

The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We de...

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Published in:	Clinical Immunology Vol. 120; no. 2; pp. 138 - 146
Main Authors:	Montoya, Carlos Julio, Velilla, Paula Andrea, Chougnet, Claire, Landay, Alan L., Rugeles, Maria Teresa
Format:	Journal Article
Language:	English
Published:	San Diego, CA Elsevier Inc 01.08.2006 Elsevier
Subjects:	Adult Antigens, CD - blood Antigens, Differentiation, T-Lymphocyte - blood B7-2 Antigen - blood Biological and medical sciences CD3 Complex - biosynthesis CD3+/CD56+ cells CD56 Antigen - biosynthesis Female Fundamental and applied biological sciences. Psychology Fundamental immunology HIV Infections - immunology HIV Seronegativity - immunology HIV-1 HIV-1 - immunology HIV-1-exposed seronegatives Human immunodeficiency virus 1 Humans IFN-γ Immunity Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Immunophenotyping Innate immunity Interferon-gamma - biosynthesis Invariant NKT cells Killer Cells, Natural - immunology Lectins, C-Type Male Medical sciences Middle Aged NK cells Up-Regulation HIV-1 CD3+/CD56+ cells Invariant NKT cells NK cells IFN-γ HIV-1-exposed seronegatives Innate immunity Human Immunopathology Invariant Natural killer T cell HIV-1 virus Retroviridae Natural immunity AIDS Immune deficiency Lentivirus Infection Virus Natural killer cell Immunology Viral disease Human immunodeficiency virus Gamma interferon
ISSN:	1521-6616, 1521-7035, 1365-2567
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Abstract	The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-α was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-γ by PMA/Ionomycin-activated CD56bright NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-γ are well established, and so our results suggest that IFN-γ production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection.
AbstractList	The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN- alpha was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN- gamma by PMA/Ionomycin-activated CD56 super(b) super(r) super(i) super(g) super(h) super(t) NK cells and CD3+ /CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN- gamma are well established, and so our results suggest that IFN- gamma production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection. The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-alpha was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-gamma by PMA/Ionomycin-activated CD56(bright) NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-gamma are well established, and so our results suggest that IFN-gamma production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection. The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-α was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-γ by PMA/Ionomycin-activated CD56bright NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-γ are well established, and so our results suggest that IFN-γ production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection. The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-alpha was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-gamma by PMA/Ionomycin-activated CD56(bright) NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-gamma are well established, and so our results suggest that IFN-gamma production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection.The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural resistance exhibited by individuals who are continuously exposed to HIV-1 but remain seronegative (ESN) has not been thoroughly evaluated. We determined the frequency and function of peripheral blood innate immune cells (plasmacytoid and myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative individuals. ESN demonstrated a similar frequency of innate immune cells in comparison to controls and a higher frequency of dendritic cells, NK and invariant NKT cells compared to HIV-1-infected subjects. Incubation of mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to a similar degree on innate cells from the three study groups. CpG ODN-stimulated secretion of cytokines was also similar between ESN and controls, while secretion of IFN-alpha was significantly decreased in HIV-1+ individuals. Importantly, expression of IFN-gamma by PMA/Ionomycin-activated CD56(bright) NK cells and CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The anti-viral effects of IFN-gamma are well established, and so our results suggest that IFN-gamma production by innate immune cells might be one of the multiple factors involved in controlling the establishment of sexually transmitted HIV-1 infection.
Author	Rugeles, Maria Teresa Montoya, Carlos Julio Velilla, Paula Andrea Landay, Alan L. Chougnet, Claire
Author_xml	– sequence: 1 givenname: Carlos Julio surname: Montoya fullname: Montoya, Carlos Julio email: cmontoya@virologia.udea.edu.co organization: Group of Immunovirology, Biogenesis Corporation, University of Antioquia, Medellin, Colombia – sequence: 2 givenname: Paula Andrea surname: Velilla fullname: Velilla, Paula Andrea organization: Group of Immunovirology, Biogenesis Corporation, University of Antioquia, Medellin, Colombia – sequence: 3 givenname: Claire surname: Chougnet fullname: Chougnet, Claire organization: Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA – sequence: 4 givenname: Alan L. surname: Landay fullname: Landay, Alan L. organization: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA – sequence: 5 givenname: Maria Teresa surname: Rugeles fullname: Rugeles, Maria Teresa organization: Group of Immunovirology, Biogenesis Corporation, University of Antioquia, Medellin, Colombia
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Keywords	HIV-1 CD3+/CD56+ cells Invariant NKT cells NK cells IFN-γ HIV-1-exposed seronegatives Innate immunity Human Immunopathology Invariant Natural killer T cell HIV-1 virus Retroviridae Natural immunity AIDS Immune deficiency Lentivirus Infection Virus Natural killer cell Immunology Viral disease Human immunodeficiency virus Gamma interferon
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Snippet	The mechanisms involved in controlling the establishment of HIV-1 infection are not fully understood. In particular, the role of innate immunity in natural...
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SubjectTerms	Adult Antigens, CD - blood Antigens, Differentiation, T-Lymphocyte - blood B7-2 Antigen - blood Biological and medical sciences CD3 Complex - biosynthesis CD3+/CD56+ cells CD56 Antigen - biosynthesis Female Fundamental and applied biological sciences. Psychology Fundamental immunology HIV Infections - immunology HIV Seronegativity - immunology HIV-1 HIV-1 - immunology HIV-1-exposed seronegatives Human immunodeficiency virus 1 Humans IFN-γ Immunity Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Immunophenotyping Innate immunity Interferon-gamma - biosynthesis Invariant NKT cells Killer Cells, Natural - immunology Lectins, C-Type Male Medical sciences Middle Aged NK cells Up-Regulation
Title	Increased IFN-γ production by NK and CD3+/CD56+ cells in sexually HIV-1-exposed but uninfected individuals
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