Preferential Destruction of Interstitial Macrophages over Alveolar Macrophages as a Cause of Pulmonary Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

To our knowledge, this study demonstrates for the first time that the AIDS virus differentially impacts two distinct subsets of lung macrophages. The predominant macrophages harvested by bronchoalveolar lavage (BAL), alveolar macrophages (AMs), are routinely used in studies on human lung macrophages, are long-lived cells, and exhibit low turnover. Interstitial macrophages (IMs) inhabit the lung tissue, are not recovered with BAL, are shorter-lived, and exhibit higher baseline turnover rates distinct from AMs. We examined the effects of SIV infection on AMs in BAL fluid and IMs in lung tissue of rhesus macaques. SIV infection produced massive cell death of IMs that contributed to lung tissue damage. Conversely, SIV infection induced minimal cell death of AMs, and these cells maintained the lower turnover rate throughout the duration of infection. This indicates that SIV produces lung tissue damage through destruction of IMs, whereas the longer-lived AMs may serve as a virus reservoir to facilitate HIV persistence.

Increased monocyte turnover is associated with interstitial macrophage accumulation and pulmonary tissue damage in SIV-infected rhesus macaques.

We recently reported that increasing blood monocyte turnover that was associated with tissue macrophage death better predicts terminal disease progression in adult SIV-infected macaques than does declining CD4(+) T cell levels. To understand better mechanisms of pathogenesis, this study relates severity of lung-tissue damage to the ratio, distribution, and inflammatory responses of lung macrophage subsets during SIV infection in rhesus macaques exhibiting varying rates of monocyte turnover. In vivo BrdU incorporation was used to evaluate kinetics of monocyte/tissue macrophage turnover. Tissue damage was scored microscopically from H&E-stained lung-tissue sections, and cytokine expression was examined via immunohistochemistry and confocal microscopy. Increased monocyte turnover in SIV-infected rhesus macaques significantly correlated with severity of lung-tissue damage, as exhibited by perivasculitis, vasculitis, interstitial pneumonia, alveolar histiocytosis, foamy macrophages, multinucleated giant cells, fibrin, and edema in the alveoli. In addition, the higher monocyte turnover correlated with declining AI ratio, increased accumulation of IM in the perivascular region of the lung, and higher expression of IL-6 in the IM of the lung tissue exposed to a LPS, calcium ionophore, and tumor promoter combination stimulation ex vivo. Accumulation of IM associated with increasing monocyte turnover during SIV infection appears to contribute to chronic pulmonary inflammation and tissue damage during disease progression to AIDS.

Application of the diagnostic evaluation for alopecia in traditional veterinary species to laboratory rhesus macaques (Macaca mulatta).

Alopecia in nonhuman primates in the biomedical research setting is often attributed to compromised psychologic wellbeing. Behavioral causes, mainly hair plucking, have become the unconfirmed and exclusive default diagnosis, and the possibility that alopecia may be secondary to a primary medical or dermatologic disease is often overlooked. Although nonbehavioral causes of alopecia in nonhuman primates are described in the literature, few prospective hypothesis-based studies have investigated medical and behavioral etiologies concurrently. We therefore undertook such a study with the aim of designing a clinical diagnostic guide for approaching cases of nonhuman primate alopecia. Because most cases of alopecia in nonhuman primates in the literature and at our facility are not associated with a definitive diagnosis, the hypothesis we tested was that the well-established diagnostic evaluation for alopecia used for traditional veterinary species is not applicable to nonhuman primates. Discounting differences in histopathology and behavioral assessment, the current study revealed few clinically relevant significant differences between nonhuman primates with and without alopecia. As a result, our hypothesis was confirmed, and we conclude that the standard dermatologic diagnostic plan typically described for alopecia diagnosis in traditional veterinary species and used as the basis for assessment of alopecia in nonhuman primates should be reassessed.