Article

Human tissue mast cells are an inducible reservoir of persistent HIV infection

Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia, United States
Blood (Impact Factor: 10.43). 07/2007; 109(12):5293-300. DOI: 10.1182/blood-2006-11-058438
Source: PubMed

ABSTRACT We have proposed that, unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34(+) pluripotent progenitors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine coreceptors 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 antiretroviral therapy (HAART) during pregnancy. Furthermore, infectious virus, capable of infecting alloactivated 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 persons during HAART.

Download full-text

Full-text

Available from: Hong Yi, Jul 08, 2015
0 Followers
 · 
113 Views
  • Source
    • "In addition to a role in viral clearance and immune surveillance, recent work from several groups has also suggested a detrimental role for mast cells in viral infections. For instance, HIV has been shown to infect human mast cell progenitors, which can mature and develop as long-lived viral reservoirs during latent infection (Sundstrom et al. 2007). Moreover, Graham et al. (2013) observed that mast cells contributed to the establishment of IAV-induced inflammatory response and lung damage. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 07/2014; 62(10). DOI:10.1369/0022155414545334 · 1.22 Impact Factor
  • Source
    • "It has to be noted, that although most of these findings indicate a possible beneficial role for MCs in viral infection there may be circumstances in which the role of MCs could be detrimental. For example, Sundstrom et al. (2007) reported that HIV-infected human tissue MCs might comprise a long-lived inducible reservoir of persistent HIV in infected individuals. MCs co-cultured with respiratory syncytial virus (RSV)-infected A549 airway epithelial cells show degranulation and increased TNF-α secretion. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In addition to their detrimental role in allergic diseases, mast cells (MCs) are well known to be important cells of the innate immune system. In the last decade, they have been shown to contribute significantly to optimal host defense against numerous pathogens including parasites, bacteria, and viruses. The contribution of MCs to the immune responses in fungal infections, however, is largely unknown. In this review, we first discuss key features of mast cell responses to pathogens in general and then summarize the current knowledge on the function of MCs in the defense against fungal pathogens. We especially focus on the potential and proven mechanisms by which MCs can detect fungal infections and on possible MC effector mechanisms in protecting from fungal infections.
    Frontiers in Immunology 06/2012; 3:146. DOI:10.3389/fimmu.2012.00146
  • Source
    • "It has to be noted, though, that although most of these findings indicate a possible beneficial role for MCs in viral infection there may be circumstances in which the role of MCs could be detrimental. For example, Sundstrom et al. (2007) reported that HIV-infected human tissue MCs might comprise a longlived inducible reservoir of persistent HIV in infected individuals. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mast cells are not only potent effector cells in allergy, but are also important players in protective immune responses against pathogens. Most of our knowledge about mast cells in innate immunity is derived from models of sepsis, whereas their role in innate immune responses of the skin has largely been neglected in the past. Their particular pattern of distribution in the skin and their ability to sense and react to pathogens and other danger signals indicate that mast cells can be important sentinels and effector cells in skin immune responses. The recent findings reviewed here have confirmed this hypothesis and have established a prominent role for skin mast cells in innate immunity.
    Immunobiology 02/2008; 213(3-4):251-60. DOI:10.1016/j.imbio.2007.10.017 · 3.18 Impact Factor