Sex Differences in Innate Immune Responses to Bacterial Pathogens

AbstractThe mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 − < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

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Distinct Innate Immune Responses of COPD Alveolar Macrophages to Different Respiratory Bacterial Pathogens.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3951 ◽

2009 ◽

Author(s):

CS Berenson ◽

RL Clare ◽

J Maloney ◽

S Sethi

Keyword(s):

Immune Responses ◽

Alveolar Macrophages ◽

Bacterial Pathogens ◽

Innate Immune ◽

Innate Immune Responses

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Hacking the host: exploitation of macrophage polarization by intracellular bacterial pathogens

Pathogens and Disease ◽

10.1093/femspd/ftaa009 ◽

2020 ◽

Vol 78 (1) ◽

Cited By ~ 5

Author(s):

Joseph D Thiriot ◽

Yazmin B Martinez-Martinez ◽

Janice J Endsley ◽

Alfredo G Torres

Keyword(s):

Immune Responses ◽

Bacterial Pathogens ◽

Macrophage Polarization ◽

Polarization State ◽

Innate Immune ◽

Innate Immune Responses ◽

Host Defenses ◽

M2 Polarization ◽

Integral Role ◽

Macrophage Plasticity

ABSTRACT Macrophages play an integral role in host defenses against intracellular bacterial pathogens. A remarkable plasticity allows for adaptation to the needs of the host to orchestrate versatile innate immune responses to a variety of microbial threats. Several bacterial pathogens have adapted to macrophage plasticity and modulate the classical (M1) or alternative (M2) activation bias towards a polarization state that increases fitness for intracellular survival. Here, we summarize the current understanding of the host macrophage and intracellular bacterial interface; highlighting the roles of M1/M2 polarization in host defense and the mechanisms employed by several important intracellular pathogens to modulate macrophage polarization to favor persistence or proliferation. Understanding macrophage polarization in the context of disease caused by different bacterial pathogens is important for the identification of targets for therapeutic intervention.

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Innate immune responses of epithelial cells following infection with bacterial pathogens

Current Opinion in Immunology ◽

10.1016/s0952-7915(00)00235-1 ◽

2001 ◽

Vol 13 (4) ◽

pp. 410-416 ◽

Cited By ~ 102

Author(s):

Dana J Philpott ◽

Stephen E Girardin ◽

Philippe J Sansonetti

Keyword(s):

Epithelial Cells ◽

Immune Responses ◽

Bacterial Pathogens ◽

Innate Immune ◽

Innate Immune Responses

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Sex differences in innate anti-viral immune responses to respiratory viruses

10.1101/2020.09.18.20195784 ◽

2020 ◽

Author(s):

Eteri Regis ◽

Sara Fontanella ◽

Lijing Lin ◽

Rebecca Howard ◽

Sadia Haider ◽

...

Keyword(s):

Sex Differences ◽

Immune Responses ◽

Mononuclear Cells ◽

Respiratory Viruses ◽

Innate Immune ◽

Morbidity And Mortality ◽

High Morbidity ◽

Innate Immune Responses ◽

Peripheral Blood Mononuclear ◽

Syncytial Virus

Males have excess morbidity and mortality from respiratory viral infections and especially so in COVID-19. The mechanisms explaining this excess in disease burden in males are unknown. Innate immune responses are likely critical in protection against a novel virus like SARS-CoV-2. We hypothesised that innate immune responses may be deficient in males relative to females. To test this we stimulated peripheral blood mononuclear cells (PBMCs) from participants in a population-based birth cohort with three respiratory viruses (rhinoviruses-RV-A16 and RV-A1, and respiratory syncytial virus-RSV) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2). We measured interferon (IFN) and IFN-induced chemokine responses and investigated sex differences in virus-induced responses. IFN-α, IFN-β and IFN-γ responses to RV-A16 were deficient in males compared to females, fold-inductions being 1.92-fold (P<0.001), 2.04-fold (P<0.001) and 1.77-fold (P=0.003) lower in males than females, respectively. Similar significant deficiencies in innate immune responses were observed in males for eleven other cytokine-stimulus pairs. Responses in males were greater than those in females in only one of 35 cytokine-stimulus pairs investigated. Review of healthcare records revealed that 12.1% of males but only 6.6% of females were admitted to hospital with respiratory infections in the first year of life (P=0.017). Impaired innate anti-viral immunity in males likely results in high morbidity and mortality from respiratory viruses including COVID-19. Males may preferentially benefit from therapies that boost innate anti-viral immune responses.

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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