Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Sui, Yongjun; Li, Shanping; Pinson, David M.; Adany, Istvan; Li, Zhuang; Villinger, François; Narayan, Opendra; Buch, Shilpa

doi:10.1016/s0002-9440(10)62259-6

Cited by 23 publications

(24 citation statements)

References 34 publications

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“…Consistent with our findings here, CCL2 and CXCL10 in rhesus macaques infected with simian/human immunodeficiency virus is strongly associated with the development of pneumonia. 52 Similarly, CXCL9 and CXCL10 were found by us through microarray analyses to be up-regulated in rhesus macaque lung tissues. 13 Taken altogether, our data strongly suggest that P. carinii is involved in induction of these chemokines.…”

Section: Discussionmentioning

confidence: 80%

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

Qin

Junecko

Trichel

et al. 2010

The American Journal of Pathology

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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.

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Section: Discussionmentioning

confidence: 80%

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

Qin

Junecko

Trichel

et al. 2010

The American Journal of Pathology

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“…The dramatic effect of host factors on replication of the virus was identified in our subsequent studies. In previous reports, we (26,33) have shown that monocyte chemotactic protein-1 (MCP-1), CXC chemokine ligand 10 (CXCL10), interleukin-4 (IL-4), and platelet-derived growth factor (PDGF) caused enhancement of viral replication in macrophages, and these cytokines were found in abundance in inflamed virus-infected lungs of macaques (8,11,33).…”

Section: Pneumonia Is a Major Complication Of Human Immunodeficiency mentioning

confidence: 99%

“…Immunohistochemical analyses were carried out on paraffin-fixed tissue sections of lung as described earlier (33). To detect the presence of macrophages, sections were treated with murine monoclonal antibodies, HAM 56 (Dako, Carpenteria, CA).…”

Section: Animalsmentioning

confidence: 99%

“…Plasma viral RNA concentrations were assessed by real-time RT-PCR as previously described (33). Briefly, virus was pelleted from 1 ml of EDTA-anticoagulated clarified plasma for 1 h by centrifugation at 20,000 g at 4°C.…”

Section: Animalsmentioning

confidence: 99%

“…Since MCP-1, also termed macrophage chemotactic and activating factor (MCAF/CCL2), and its receptor, CCR2, are reported to contribute to progressive fibrosis (16,24,27,39), and since MCP-1 also plays an important role in promoting virus replication in infected MDMs and in macaques with SHIV-associated pneumonia (15,32,33), we determined whether levels of MCP-1 in lung homogenates and the immunohistochemical expression of its receptor, CCR2, in lung sections were elevated in the SHIV-BL animals. The study showed that there was a statistically significant difference in MCP-1 in lung homogenates between the two groups of animals: treated with bleomycin and untreated with bleomycin (P ϭ 0.0357; Fig.…”

Section: Mcp-1/ccr2 Expression In the Lungs Of Shiv-infected Macaquesmentioning

confidence: 99%

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Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

Dhillon¹,

Pinson²,

Dhillon³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pneumonia is a major complication of human immunodeficiency virus (HIV) pathogenesis but it develops only after prolonged infection. We used the macaque model to explore a hypothesis that the disease is a two-stage process, the first stage being establishment of the viral infection in the lung and the second being amplification of virus replication by host factors induced by chemical agents or opportunistic pathogens in the lung. Bleomycin, a chemical known to induce diffuse alveolar damage and pulmonary fibrosis with accumulation of macrophages and a rich T helper type 2 (Th2) cytokine environment, was inoculated intratracheally into five of eight SHIV 89.6P-infected macaques and into one uninfected macaque. Three additional simian HIV (SHIV)-infected macaques without bleomycin treatment served as untreated virus controls. Although none of the animals became clinically ill, bleomycin induced classical host responses in the lungs of all the treated, virus-infected macaques. There was enhanced production of the chemokine, monocyte chemotactic protein-1 (MCP-1), that had previously been shown to cause enhanced replication of the virus. Four of the five treated animals developed more productive SHIV infection in the lungs compared with the infected untreated animals. Enhanced virus replication was found primarily in infiltrating macrophages. Enhanced replication of the virus in the lungs was associated with host factors induced by the drug and supported the hypothesis for a two-stage process of pulmonary pathogenesis.

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CCL2: A potential prognostic marker and target of anti‐inflammatory strategy in HIV/AIDS pathogenesis

et al. 2011

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Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ligands and a divergent role of C-C chemokines in HIV-1 pathogenesis has been established. For example, CCL3 (MIP-1a), CCL4 (MIP-1b) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV-1 co-receptor CCR5, whereas CCL2, a proinflammatory chemokine, supports HIV-1 replication despite being a member of same chemokine family. Furthermore, the well-established role of CCL2 in driving the Th2 immune response supports its potential role in HIV-1/AIDS. Recent reports suggest multiple pathways of CCL2 affect HIV-1 infection. In this review, we provide a comprehensive overview of the role and potential mechanisms of the HIV-1-CCL2 interplay in driving virus-induced immuno-pathology, suggesting that CCL2 could be an anti-inflammatory target in the treatment of HIV-1 infection.

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Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Cited by 23 publications

References 34 publications

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

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

Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

CCL2: A potential prognostic marker and target of anti‐inflammatory strategy in HIV/AIDS pathogenesis

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