Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques

Abstract

Infection by HIV-1 frequently leads to pulmonary complications, including alterations to local immune environments. To better understand these alterations, we have examined in detail the patterns and levels of expression of chemokine, cytokine, and chemokine receptor mRNAs in lung tissues from 16 uninfected or simian immunodeficiency virus ( Pulmonary diseases are frequent complications of HIV-1 infection, affecting 75% to 85% of patients with AIDS.1 In addition, Pneumocystis carinii (now called Pneumocystis jirovecii in humans) pneumonia (PCP) is one of most frequent pulmonary opportunistic infections in HIV-1 infected individuals. However, little is known about the mechanisms leading to changes in pulmonary immune function and how these changes ultimately contribute to pathogenesis. Identifying alterations of overall immune function and the local mediators of these changes in the lungs during HIV-1 infection and AIDS will be useful for understanding and treating HIV-1-associated pulmonary complications.Chemokines are soluble immune factors that recruit cells bearing appropriate receptors into local environments as part of homeostatic immune cell trafficking and inflammatory reactions. There are approximately 50 known chemokines and 18 chemokine receptors.2 Chemokines play an important role in the control of infectious agents by recruiting effector cells to local inflammatory sites of infection and by serving directly as antimicrobial peptides.

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…These studies are further complicated by alterations in the lung environment associated with changes in immune status (immunocompetent versus immunosuppressed) and the presence of coinfection (e.g., HIV). Comprehensive evaluations of the effects of Pneumocystis on gene expression of AMs and lung tissue are beginning to address the complexity of the host-pathogen interaction (37,248). In this regard, in order to assess the influence of Pneumocystis in the lung in the association with SIV infection, Qin et al evaluated cytokine and chemokine gene expression changes in lung tissue in SIV-infected macaques with and without PCP (248).…”

“…Comprehensive evaluations of the effects of Pneumocystis on gene expression of AMs and lung tissue are beginning to address the complexity of the host-pathogen interaction (37,248). In this regard, in order to assess the influence of Pneumocystis in the lung in the association with SIV infection, Qin et al evaluated cytokine and chemokine gene expression changes in lung tissue in SIV-infected macaques with and without PCP (248). The most upregulated immune genes were found to be those for IFN-␥, IFN-␥-inducible CXCR3, CCR5 ligands, and their cognate chemokine receptors.…”

Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice

“…The potential role of chemokines in Pneumocystis infection has been examined in a number of in vitro and in vivo studies [5-16]. In vitro studies have demonstrated an increase in Cxcr2 ligands [6, 17], while in vivo studies, which were primarily performed in immunosuppressed mice, have shown increased expression of Ccr2, Ccr5, and Cxcr3 ligands [9-11, 14, 15, 18]. However, no study to date has comprehensively examined chemokine and chemokine receptor responses in immunocompetent hosts.…”

Macaque Paneth Cells Express Lymphoid Chemokine CXCL13 and Other Antimicrobial Peptides Not Previously Described as Expressed in Intestinal Crypts

“…), which was defined by weight loss, loss of CD4 ϩ T lymphocytes, and/or development of opportunistic infections, such as Pneumocystis jirovecii pneumonia. These animals and their clinicovirologic states have been presented previously (12)(13)(14).…”

“…Adult cynomolgus macaques (Macaca fascicularis) were used in this study and were inoculated intrarectally with the pathogenic SIV/DeltaB670 isolate (11). These animals and their clinicovirologic states have been described previously (12)(13)(14). Fixation and processing of tissues at necropsy were completed as described previously (15).…”