Sex-specific innate immune selection of HIV-1in utero is associated with increased femalesusceptibility to infection

Sex-specific innate immune selection of HIV-1in utero is associated with increased femalesusceptibility to infection

Fecha de publicación online: 14/04/2020 Revista: Nature Communications

Abstract:

Female children and adults typically generate more efficacious immune responses to vaccinesand infections than age-matched males, but also suffer greater immunopathology and auto-immune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants fromKwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5–2-fold increasedfemale susceptibility to intrauterine HIV infection. Viruses transmitted to females have lowerreplicative capacity (p=0.0005) and are more type I interferon-resistant (p=0.007) thanthose transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordanttwins are more activated (p=0.01) and more susceptible to HIV infection in vitro (p=0.03).Sex differences in outcome include superior maintenance of aviraemia among males (p=0.007) that is not explained by differential antiretroviral therapy adherence. These datademonstrate sex-specific innate immune selection of HIV associated with increased femalesusceptibility to in utero infection and enhanced functional cure potential among infected males.

Autores: Emily Adland, Jane Millar, Nomonde Bengu, Maximilian Muenchhoff, Rowena Fillis, Kenneth Sprenger, Vuyokasi Ntlantsana, Julia Roider, Vinicius Vieira, Katya Govender, John Adamson, Nelisiwe Nxele, Christina Ochsenbauer, John Kappes, Luisa Mori, Jeroen van Lobenstein, Yeney Graza, Kogielambal Chinniah, Constant Kapongo, Roopesh Bhoola, Malini Krishna, Philippa C. Matthews, Ruth Penya Poderos, Marta Colomer Lluch, Mari Carmen Puertas, Julia G. Prado, Neil McKerrow, Moherndran Archary, Thumbi Ndung’u, Andreas Groll, Pieter Jooste, Javier Martinez-Picado, Marcus Altfeld &​ Philip Goulder   

Suscríbete a la newsletter

Back to Top
Irsi Caixa

Impulsado por:

Fundación 'La Caixa' Generalitat de Catalunya - Departament de Salut

 

HR Excellence in Research

Miembro de:

Cerca

Con la colaboración de: