Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS

Kornfeld, Christopher; Ploquin, Mickaël J.-Y.; Pandrea, Ivona; Faye, Abdourahmane; Onanga, Richard; Apetrei, Cristian; Poaty‐Mavoungou, Virginie; Rouquet, Pierre; Estaquier, Jérǒme; Mortara, Lorenzo; Desoutter, Jean-François; Butor, Cécile; Grand, Roger Le; Roques, Pierre; Simon, François; Barré‐Sinoussi, Françoise; Diop, Ousmane M.; Müller‐Trutwin, Michaela

doi:10.1172/jci23006

Cited by 225 publications

(126 citation statements)

References 48 publications

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“…A comparison of transcriptional profiles of nonprogressive and progressive SIV infections has revealed differences in transcriptional kinetics in lymphoid tissues (16). The gene expression patterns in progressive infection exhibit a shift toward general Th1 immune responses with strong and sustained IFN type I and II responses, loss of T regulatory cells, and loss of control of T cell activation (17)(18)(19). Although the magnitudes of systemic immune activation at the time of acute infection are comparable between nonprogressive and progressive SIV infections at the gene expression level, cytokine/chemokine protein levels have not been extensively tested (16).…”

mentioning

confidence: 99%

Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Keating

Heitman

et al. 2016

J Virol

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Acute human immunodeficiency virus (HIV) infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in nonpro- IMPORTANCENHP models of HIV infection constitute a powerful tool with which to study viral pathogenesis in order to gain critical information for a better understanding of HIV infection in humans. Here we studied progressive and nonprogressive simian immunodeficiency virus (SIV) infection models in both natural and nonnatural host NHP species. Regardless of the pathogenicity of the virus infection and regardless of the NHP species studied, the magnitude of viremia, as measured by area under the curve, during the first 4 weeks of infection correlated positively with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between nonprogressive and progressive SIV infection models. The qualitative differences in the early immune response in pathogenic and nonpathogenic infections identified here may be important determinants of the subsequent disease course.

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mentioning

confidence: 99%

Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Keating

Heitman

et al. 2016

J Virol

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“…Similarly rapid and robust adaptive CD8 T cell responses correlate with improved outcomes of LCMV infection in mice and simian immunodeficiency virus (SIV) infection in macaques (2). TGF-␤ is a major immunosuppressive cytokine that limits innate (DC and NK cell) and adaptive immunity in vitro and in vivo in different systems, with high levels of TGF-␤ correlating with enhanced susceptibility to virus and viral persistence for HCV in humans and SIV in rhesus macaques (64,65) as well as LCMV and the malaria parasite in mice (6,7).…”

Section: Discussionmentioning

confidence: 99%

“…5F). The secretion of IFN-␥, TNF-␣, and IL-2 upon ex vivo GP [33][34][35][36][37][38][39][40][41] or GP [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] peptide stimulation was similar in CD8 and CD4 T cells from WT and CD11c-dnTGF-␤RII mice (Fig. 5G).…”

Section: Increased Nk Cell (But Not Dc) Responses During Lcmv Cl13 Inmentioning

confidence: 99%

Constitutive but Not Inducible Attenuation of Transforming Growth Factor β Signaling Increases Natural Killer Cell Responses without Directly Affecting Dendritic Cells Early after Persistent Viral Infection

Lewis

Macal

Hesser

et al. 2015

J Virol

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Rapid innate responses to viral encounters are crucial to shaping the outcome of infection, from viral clearance to persistence. Transforming growth factor ␤ (TGF-␤) is a potent immune suppressor that is upregulated early upon viral infection and maintained during chronic infections in both mice and humans. However, the role of TGF-␤ signaling in regulating individual cell types in vivo is still unclear. Using infections with two different persistent viruses, murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV; Cl13), in their natural rodent host, we observed that TGF-␤ signaling on dendritic cells (DCs) did not dampen DC maturation or cytokine production in the early stages of chronic infection with either virus in vivo. In contrast, TGF-␤ signaling prior to (but not during) chronic viral infection directly restricted the natural killer (NK) cell number and effector function. This restriction likely compromised both the early control of and host survival upon MCMV infection but not the long-term control of LCMV infection. These data highlight the context and timing of TGF-␤ signaling on different innate cells that contribute to the early host response, which ultimately influences the outcome of chronic viral infection in vivo. IMPORTANCEIn vivo host responses to pathogens are complex processes involving the cooperation of many different immune cells migrating to specific tissues over time, but these events cannot be replicated in vitro. Viruses causing chronic infections are able to subvert this immune response and represent a human health burden. Here we used two well-characterized viruses that are able to persist in their natural mouse host to dissect the role of the suppressive molecule TGF-␤ in dampening host responses to infection in vivo. This report presents information that allows an increased understanding of long-studied TGF-␤ signaling by examining its direct effect on different immune cells that are activated very early after in vivo viral infection and may aid with the development of new antiviral therapeutic strategies.T he coordinated effort of both the innate and the adaptive immune systems is necessary to control invasive pathogens. Rapid viral dissemination has been associated with weak host antiviral responses and viral persistence in both mice and humans (1, 2). Thus, the magnitude of initial innate responses can be critical to limit the establishment of potentially chronic infections. Human chronic infections with hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and Mycobacterium tuberculosis as well as mouse infections with lymphocytic choriomeningitis virus (LCMV) and the malaria parasite are associated with the increased production and/or signaling of the immunosuppressive molecule transforming growth factor ␤ (TGF-␤) in immune cells (3-7). However, the precise role of TGF-␤-mediated suppression on innate and adaptive immune components during infection has not been fully deciphered.Among innate cells, dendritic cells (DC...

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“…The initial studies of natural SIV infections were performed during chronic infection and were not able to inform early events. Indeed, more recent studies designed to characterize the acute phase of SIV infection consistently show that, as described for progressive infection, nonprogressive SIV infection is also associated with an early increase in T cell proliferation and activation Kornfeld et al, 2005; I. V. Pandrea et al, 2007b;Silvestri et al, 2005). This phenotype is very common among several natural hosts, even those less characterized than sooty mangabeys and African green monkeys.…”

Section: Absence Of Chronic Immune Activationmentioning

confidence: 90%

“…This phenotype is very common among several natural hosts, even those less characterized than sooty mangabeys and African green monkeys. For instance, transient levels of immune activation have been described in Mandrills, in which CD4 and CD8 HLA-DR+ cells at first increase but then return to normal levels by day 60 post-infection (Onanga et al, 2006), as well as in Caribbean African green monkeys, which show a rapid increase in CD8 HLA-DR+ T cells and then a rapid return to baseline 2-3 weeks post-infection, while having no changes in CD4 HLA-DR+ T cell frequencies (Kornfeld et al, 2005;I. Pandrea et al, 2006).…”

Section: Absence Of Chronic Immune Activationmentioning

confidence: 99%

HIV Without AIDS: The Immunological Secrets of Natural Hosts

Ende¹,

Bonkosky²,

Paiardini³

2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

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Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS

Cited by 225 publications

References 48 publications

Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

Constitutive but Not Inducible Attenuation of Transforming Growth Factor β Signaling Increases Natural Killer Cell Responses without Directly Affecting Dendritic Cells Early after Persistent Viral Infection

HIV Without AIDS: The Immunological Secrets of Natural Hosts

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