Sex differences in HIV-1-mediated immunopathology

Ziegler, Susanne; Altfeld, Marcus

doi:10.1097/coh.0000000000000237

Cited by 41 publications

(40 citation statements)

References 71 publications

(86 reference statements)

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“…Meta-analysis data indicates 41% less HIV RNA in women compared to men following primary infection, which gradually increase to a higher viral load set point compared to males after chronic infection (149–151). In females, HIV-1 promotes type 1 IFN production by pDCs via TLR7 signaling, which itself is increased downstream of E3 signaling (115, 152).…”

Section: Rna Virusesmentioning

confidence: 99%

“…Follow up studies have shown that even with same viral load pDCs obtained from females showed higher CD8+ T cell activation compared to men (115). Additionally, females mount a stronger B and T cell activation following HIV-1 infection due to higher baseline count of CD4 + T and CD8 + T cells in women as compared to men (115, 151). The concentration of estrogen binding SHBG is increased in HIV infected male individuals.…”

Section: Rna Virusesmentioning

confidence: 99%

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Sex Drives Dimorphic Immune Responses to Viral Infections

Ghosh

Klein

2017

The Journal of Immunology

197

158

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New attention to sexual dimorphism in normal mammalian physiology and disease has uncovered a previously unappreciated breadth of mechanisms by which females and males differentially exhibit quantitative phenotypes. Thus, in addition to the established modifying effects of hormones, which prenatally and post-pubertally pattern cells and tissues in a sexually dimorphic fashion, sex differences are caused by extra-gonadal and dosage effects of genes encoded on sex chromosomes. Sex differences in immune responses, especially during autoimmunity, have been studied predominantly within the context of sex hormone effects. More recently, immune response genes have been localized to sex chromosomes themselves or found to be regulated by sex chromosome genes. Thus, understanding how sex impacts immunity requires the elucidation of complex interactions between sex hormones, sex chromosomes and immune response genes. In this brief review, we discuss current knowledge and new insights into these intricate relationships in the context of viral infections.

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Section: Rna Virusesmentioning

confidence: 99%

Section: Rna Virusesmentioning

confidence: 99%

Sex Drives Dimorphic Immune Responses to Viral Infections

Ghosh

Klein

2017

The Journal of Immunology

197

158

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“…Most human immunological studies during AHI have been done in resource-rich countries in patients infected with HIV subtype B, yet HIV-1 subtypes differ in their virulence [1,[23][24][25]. Also, the previous studies were mostly conducted in cohorts that were dominated by male patients, yet the highest burden of HIV in sub-Saharan Africa is in women, and gender has been shown to affect inflammatory responses [26]. Furthermore, geographical localization determines the basal inflammatory state due to environmental exposure to other endemic pathogens [27].…”

Section: Introductionmentioning

confidence: 99%

Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection

Muema

Akilimali

Ndumnego

et al. 2020

BMC Med

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Introduction: Immunological damage in acute HIV infection (AHI) may predispose to detrimental clinical sequela. However, studies on the earliest HIV-induced immunological changes are limited, particularly in sub-Saharan Africa. We assessed the plasma cytokines kinetics, and their associations with virological and immunological parameters, in a well-characterized AHI cohort where participants were diagnosed before peak viremia. Methods: Blood cytokine levels were measured using Luminex and ELISA assays pre-infection, during the hyperacute infection phase (before or at peak viremia, 1-11 days after the first detection of viremia), after peak viremia (24-32 days), and during the early chronic phase (77-263 days). Gag-protease-driven replicative capacities of the transmitted/founder viruses were determined using a green fluorescent reporter T cell assay. Complete blood counts were determined before and immediately following AHI detection before ART initiation. Results: Untreated AHI was associated with a cytokine storm of 12 out of the 33 cytokines analyzed. Initiation of ART during Fiebig stages I-II abrogated the cytokine storm. In untreated AHI, virus replicative capacity correlated positively with IP-10 (rho = 0.84, P < 0.001) and IFN-alpha (rho = 0.59, P = 0.045) and inversely with nadir CD4 + T cell counts (rho = − 0.58, P = 0.048). Hyperacute HIV infection before the initiation of ART was associated with a transient increase in monocytes (P < 0.001), decreased lymphocytes (P = 0.011) and eosinophils (P = 0.003) at Fiebig stages I-II, and decreased eosinophils (P < 0.001) and basophils (P = 0.007) at Fiebig stages III-V. Levels of CXCL13 during the untreated hyperacute phase correlated inversely with blood eosinophils (rho = − 0.89, P < 0.001), basophils (rho = − 0.87, P = 0.001) and lymphocytes (rho = − 0.81, P = 0.005), suggesting their trafficking into tissues. In early treated individuals, time to viral load suppression correlated positively with plasma CXCL13 at the early chronic phase (rho = 0.83, P = 0.042). Conclusion: While commencement of ART during Fiebig stages I-II of AHI abrogated the HIV-induced cytokine storm, significant depletions of eosinophils, basophils, and lymphocytes, as well as transient expansions of monocytes, were still observed in these individuals in the hyperacute phase before the initiation of ART, suggesting that even ART initiated during the onset of viremia does not abrogate all HIV-induced immune changes.

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“…Interventions in NHP studies have elucidated the role of IFN and microbial translocation, although these studies may not always be reproducible in humans given the complexity of human infection with various comorbities, genetics and life style factors. Sex differences in innate immune sensing and IFN responses by pDCs can also have a critical role in determining differences in HIV-1 disease manifestations between women and men during acute and chronic infection, and require further studying [15]. Cardiovascular disease [16] and neurocognitive disease [17] represent important morbidities in treated patients with HIV-1 infection and have been linked to both adaptive and innate immune activation.…”

mentioning

confidence: 99%