Differential Susceptibility to Infectious Respiratory Diseases between Males and Females Linked to Sex-Specific Innate Immune Inflammatory Response

Abstract

It is widely acknowledged that males and females exhibit contrasting degrees of susceptibility to infectious and non-infectious inflammatory diseases. This is particularly observed in respiratory diseases where human males are more likely to be affected by infection-induced acute inflammations compared to females. The type and magnitude of the innate immune inflammatory response play a cardinal role in this sex bias. Animal models mimicking human respiratory diseases have been used to address the biological factors that could explain the distinct outcomes. In this review, we focus on our current knowledge about experimental studies investigating sex-specific differences in infection-induced respiratory diseases and we provide an update on the most important innate immune mechanisms that could explain sex bias of the inflammatory response. We also discuss whether conclusions drawn from animal studies could be relevant to human.

COVID-19 and Sex-/Gender-Specific Differences: Understanding the Discrimination

“…23,25,31 Fetal-placental programming, genetic variation, and sex hormones can play a role in shaping the sex-specific innate and adaptive immune inflammatory responses. 23,24,30,[32][33][34][35] In support of this, a study analyzing serum from 331 hospitalized patients found that most female patients with severe COVID-19 had more than 100 AU/mL of SARS-CoV-2 IgG antibodies, while most male patients had less than 100 AU/mL. 36 Additionally, females generated a stronger IgG production early on in the disease course compared with male patients, which is consistent with preexisting literature.…”

Sexual Dimorphism in Immune Development and in Response to Nutritional Intervention in Neonatal Piglets

“…Sex plays a role in innate, humoral, and cell-mediated immunity. It is well-established that adult males are more susceptible to infectious disease (1) and generate less reactive immune profiles (2,3), whereas adult females are more susceptible to inflammation and autoimmunity (4,5) but fare better when it comes to infectious disease (6). Females are reported to generate significantly higher levels of protective antibodies and cellmediated immunity following viral vaccinations against measles, rubella, rabies, smallpox, dengue, mumps, influenza, yellow fever, and hepatitis A and B (7)(8)(9).…”

Gender differences in bronchiectasis: a real issue?

“…Lung physiology, and specifically microbiota composition, affects the severity and progression of chronic respiratory disease states with observed gender differences [ 1 , 38 ]. The respiratory microbiome appears to have sex-specific signatures and is susceptible to a range of host immune and inflammatory consequences [ 39 , 40 ]. Continuous chronic inflammation is reported as more deleterious in females potentially contributing to greater tissue damage and their observed worse disease severity [ 41 ].…”