Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus

Abstract

Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection thatcan occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3 ؉ T cells and IBA1 ؉ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.

Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress

“…Given that the gut contains the largest quantity of lymphoid tissue within the body, inflammation in proximity to the gut is to be expected, as has been reported in HIV and SIV infections (32). Given that the gut contains the largest quantity of lymphoid tissue within the body, inflammation in proximity to the gut is to be expected, as has been reported in HIV and SIV infections (32).…”

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

“…Iba1 is a microglia/macrophage-specific calcium-binding protein (14). An activation of Iba1 macrophages in duodenum, ileum, and colon was already documented by Orandle et al (29) in macaques during the acute stage of simian immunodeficiency virus infection. In this study, we validated the role of Iba1 as marker of fetal gut inflammation reflecting an increase in M1, but not in M2, type macrophages showing that even a low-dose LPS exposure in utero near-term results in macrophage activation and increased gut leakiness (12).…”

Viral Diseases of Nonhuman Primates

“…Peripheral neuropathy is the most frequent neurologic complication associated with HIV. A ganglionitis has been described in the trigeminal ganglion and the myenteric plexus of SIV infected macaques (Laast et al, 2007;Orandle et al, 2007). This lesion is characterized by the presence of multifocal mononuclear infiltrates, primarily macrophages and lesser numbers of lymphocytes, accompanied by neuronophagia and neuronal loss.…”

“…The presence of trigeminal ganglionitis is not necessarily associated with concurrent encephalitis (Laast et al, 2007). Ganglionitis of the myenteric plexus may compromise intestinal innervation and contribute to the pathogenesis of SIV/HIV enteropathy (Orandle et al, 2007). Additional contributors to virus-associated peripheral neuropathies in HIV patients include toxic neuropathy from antiretroviral drugs, a diffuse infiltrative lymphocytosis syndrome (DILS), and inflammatory polyneuropathies associated with OI.…”