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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5293-5300.
Prepublished online as a Blood First Edition Paper on March 9, 2007; DOI 10.1182/blood-2006-11-058438.
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Submitted November 29, 2006
Accepted March 5, 2007
Human tissue mast cells are an inducible reservoir of persistent HIV infection
J. Bruce Sundstrom*, Jane E. Ellis, Gregory A. Hair, Arnold S. Kirshenbaum, Dean D. Metcalfe, Hong Yi, Adriana C. Cardona, Michael K. Lindsay, and Aftab A. Ansari
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, United States
Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD, United States
School of Medicine Microscopy Core, Emory University School of Medicine, Atlanta, GA, United States
* Corresponding author; email: jsundst{at}emory.edu.
We have proposed that unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34+ pluripotent precursors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine co-receptors necessary for viral entry and develop into long-lived, latently infected mature tissue mast cells (MCs), resistant to new infection. In vivo recruitment of prMCs to different tissue compartments occurs in response to tissue injury, growth and remodeling or allergic inflammation, allowing populations of circulating and potentially HIV-susceptible prMCs to spread persistent infection to diverse tissue compartments. In this report we provide in vivo evidence to confirm this model by demonstrating that HIV-infected women have both circulating prMCs and placental tissue MCs (PLMCs) that harbor inducible infectious HIV even after highly active anti-retroviral therapy (HAART) during pregnancy. Furthermore, infectious virus, capable of infecting allo-activated fetal cord blood mononuclear cells (CBMCs), could be induced in isolated latently-infected PLMCs after weeks in culture in vitro. These data provide the first in vivo evidence that tissue MCs, developed from infected circulating prMCs, comprise a long-lived inducible reservoir of persistent HIV in infected individuals during HAART.
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