Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells

PLoS Pathogens

James F. Smith¹  Nargis Kohgadai²  Karen S. Jang³  Christina M. Stürzel³  Ruth M. Greenblatt⁴  Jan Münch⁵  Maurice M. Garcia⁶  Ma Somsouk⁶  Linda C. Giudice⁷  Christina Ochsenbauer⁷  Joseph C. Chen⁷  Martin R. Jakobsen⁷  Anders Laustsen⁷  Warner C. Greene⁸  Jennifer J. Jones⁹  Jason A. Neidleman⁹  Janis A. Müller⁹  Karthiga Thavachelvam^1,10  Avantika Chitre^1,10  Nadia R. Roan^1,10 

[1] Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America;Department of Biomedicine, Aarhus University, Aarhus, Denmark;Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America;Department of Medicine, Division of Gastroenterology, San Francisco General Hospital and University of California, San Francisco, San Francisco, CA, United States of America;Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America;Departments of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States of America;Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America;Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

关键词: T cells;    HIV infections;    HIV;    Fibroblasts;    Flow cytometry;    Estradiol;    HIV-1;    Progesterone;   

DOI  :  10.1371/journal.ppat.1006163

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells–by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV–without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors. In comparison, mucosal epithelial cells secrete antivirals and inhibit HIV infection. These data suggest that breaches in the epithelium allow external or luminal HIV to escape an antiviral environment to access the infection-favorable environment of the stromal fibroblasts, and suggest that resident fibroblasts have a central, but previously unrecognized, role in HIV acquisition at mucosal sites. Inhibiting fibroblast-mediated enhancement of HIV infection should be considered as a novel prevention strategy.

【 授权许可】

CC BY