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oai:recercat.cat:11351/51942024-12-13T11:06:13Zcom_2072_378071com_2072_378040col_2072_378097

Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa Cantero Perez, Jon Grau Exposito, Judit Serra Peinado, Carla Rosero, Daniela A. Luque Ballesteros, Laura Astorga Gamaza, Antonio Castellví Vives, Josep Mañalich Barrachina, Laura Centeno Mediavilla, Maria Cristina Falcó Ferrer, Vicenç Buzón Gómez, María José Genesca Ferrer, Meritxell [Cantero-Pérez J, Grau-Expósito J, Serra-Peinado C, Rosero DA, Luque-Ballesteros L, Astorga-Gamaza A, Falcó V, Buzon MJ, Genescà M] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Malalties Infeccioses, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Mañalich-Barrachina L, Centeno-Mediavilla C] Servei de Ginecologia i Obstetrícia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Cèl·lules T Infeccions per VIH Coll uterí ANATOMY::Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes DISEASES::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections ANATOMY::Urogenital System::Genitalia::Genitalia, Female::Uterus::Cervix Uteri ANATOMÍA::sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos ENFERMEDADES::enfermedades del sistema inmune::síndromes de inmunodeficiencia::infecciones por VIH ANATOMÍA::sistema urogenital::genitales::genitales femeninos::útero::cuello del útero HIV viral reservoirs; Cervical mucosa; TRM Reservorios virales de VIH; Mucosa cervical; TRM Reservoris virals del VIH; Mucosa cervical; TRM HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues. This work was primarily supported by grants from the Spanish "Ministerio de Economia y Competitividad, Instituto de Salud Carlos III" (ISCIII, PI14/01235 and PI17/01470) and a fellowship award from the Dexeus foundation for women's health research to M.G., grants R21AI118411 and SAF2015-67334-R (from the Spanish Secretariat of Science and Innovation and FEDER funds) to M.J.B and grants from the ISCIII (PI14/01058 and PI17/00164) to J.G.P. M.G., M.J.B., and. J.G.P. are supported by the Spanish AIDS network Red Tematica Cooperativa de Investigacion en SIDA (RD16/0025/0007) M.G. is currently supported by the "Pla estrategic de recerca i innovacio en salut" (PERIS, SLT002/16/00353), from the Catalan government, while the Miguel Servet program from the ISCIII supports M.J.B. (CP17/00179) and J.G.P. (CP15/00014). 2020-09-01T10:33:00Z 2020-09-01T10:33:00Z 2019-10-18 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cantero-Pérez J, Grau-Expósito J, Serra-Peinado C, Rosero DA, Luque-Ballesteros L, Astorga-Gamaza A, et al. Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa. Nat Commun. 2019 Oct 18;10:4739. 2041-1723 https://hdl.handle.net/11351/5194 10.1038/s41467-019-12732-2 31628331 000490981900008 http://hdl.handle.net/11351/5194 eng Nature Communications;10 https://www.nature.com/articles/s41467-019-12732-2 info:eu-repo/grantAgreement/ES/PE2013-2016/PI14%2F01235 info:eu-repo/grantAgreement/ES/PE2017-2020/PI17%2F01470 info:eu-repo/grantAgreement/ES/PE2013-2016/PI14%2F01058 info:eu-repo/grantAgreement/ES/PE2017-2020/PI17%2F00164 info:eu-repo/grantAgreement/ES/PERIS2016-2020/SLT002%2F16%2F00353 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf application/pdf application/pdf Springer Nature Scientia