FOR 5068:  Sex differences in immunity

• Subject Area: Medicine ; Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429191104

Our immune system defends us from environmental threats, such as bacterial, parasitic and viral infections, and detects and removes abnormal cells that potentially lead to malignancies. Optimal immunological homeostasis is achieved when the threat is removed with the highest efficiency whilst avoiding collateral tissue damage for the host. This immunological balance is different between cisgender females and cisgender males (subsequently referred to as females and males). It has been shown that females mount stronger immune responses against most, but not all, pathogens compared to males, generally leading to more rapid control or clearance of infections. Females also develop stronger immunity in response to most vaccinations, and exhibit stronger immune responses against malignancies, including colorectal and lung cancers. For example, viremia is controlled at lower levels during primary HIV-1 infection in cisgender women, and lower case mortality rates were observed during COVID-19 in women compared to men. Similarly, more severe disease manifestations are observed in males during infections with Entamoeba histolytica and Mycobacterium Tuberculosis. Enhanced immune responsiveness in females, however, comes at a cost, including aggravated tissue damage, persistent inflammation and significantly higher incidences of autoimmune diseases. Examples are autoimmune diseases of the liver and the nervous system, such as primary biliary cholangitis and multiple sclerosis, that are much more common in women compared to men. Such sex-specific differences are not restricted to adults, as already boys have an increased risk for infections early in life, while girls develop a greater risk for atopic diseases around puberty. The sex bias observed in the prevalence and manifestation of some immune-mediated diseases, such as asthma, furthermore varies across the lifespan. In addition, maternal adverse events during pregnancy can interfere with the developing foetal immune system in a sex-specific manner, subsequently affecting the risks for infections later in life of the offspring. These observed differences in clinical manifestations of infectious diseases, malignancies and autoimmune diseases between females and males are widely acknowledged, whilst the underlying biological mechanisms remain incompletely understood. We here aim to address this gap in knowledge by systematically and comprehensively dissecting sex-specific immune responses in these clinical settings.

• DFG Programme: Research Units

Projects

• Coordination Funds (Applicant Altfeld, Marcus )
• Developmental origin and plasticity of sex-specific immunity against pathogens (Applicants Arck, Petra Clara ;  Stahl, Ph.D., Felix )
• Dissecting Sex Differences in the Immune Response to Vaccines (Applicant Addo, Marylyn Martina )
• Dissecting sex-specific mechanisms in T cell-mediated autoimmune neuroinflammation (Applicant Friese, Manuel A. )
• Interactions between lung microenvironment and immune responses in the sex-specific manifestation of asthma (Applicant Zazara, Dimitra )
• Investigation of sex-biased differences in anti-cancer immune responses (Applicant Loges, Sonja )
• Investigation of the impact of sex hormones on cancer immunotherapy outcome (Applicant Loges, Sonja )
• Sex-specific differences in immunity and infection: an integrative approach (Applicant Bonn, Stefan )
• Sex-specific responses of monocytes to infectious challenges (Applicant Lotter, Hannelore )
• Sex-specific responses of myeloid cells to infectious challenges (Applicants Lotter, Hannelore ;  Schneider, Bianca )
• The role of androgens in autoimmune liver diseases (Applicant Schramm, Christoph )
• The role of androgens in autoimmune liver diseases (Applicants Schramm, Christoph ;  Schwinge, Dorothee )
• Type I IFN-mediated sex differences in immune responses to HIV-1 (Applicant Altfeld, Marcus )

• Spokesperson: Professor Dr. Marcus Altfeld