Persistent accumulation of gut macrophages with impaired phagocytic function correlates with SIV disease progression in macaques.

The contribution of macrophages in the gastrointestinal tract to disease control or progression in HIV infection remains unclear. To address this question, we analyzed CD163 macrophages in ileum and mesenteric lymph nodes (LN) from SIV-infected rhesus macaques with dichotomous expression of controlling MHC class I alleles predicted to be SIV controllers or progressors. Infection induced accumulation of macrophages into gut mucosa in the acute phase that persisted in progressors but was resolved in controllers.

Widespread Virus Replication in Alveoli Drives Acute Respiratory Distress Syndrome in Aerosolized H5N1 Influenza Infection of Macaques.

Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease.

Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection.

Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the mDC response, particularly early in acute infection, is ill-defined. We studied acute pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to address this question. The mDC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response.

NK cells are required for dendritic cell-based immunotherapy at the time of tumor challenge.

Increasing evidence suggests that NK cells act to promote effective T cell-based antitumor responses. Using the B16-OVA melanoma model and an optimized Gram-positive bacteria-dendritic cell (DC) vaccination strategy, we determined that in vivo depletion of NK cells at time of tumor challenge abolished the benefit of DC immunotherapy. The contribution of NK cells to DC immunotherapy was dependent on tumor Ag presentation by DC, suggesting that NK cells act as helper cells to prime or reactivate tumor-specific T cells.

Rapid interferon-gamma release from natural killer cells induced by a streptococcal commensal.

Interferon-gamma (IFN-γ) is a critical cytokine for the initiation of immune responses against a variety of infectious agents and malignancies. We found that a range of Gram-positive and Gram-negative bacteria stimulated the rapid release (<24 h) of IFN-γ from murine leukocytes. Using fluorescence activated cell sorting and cd1d(-/-) and rag1(-/-) mice, we determined that dendritic cells (DCs) and natural killer (NK) cells were primarily responsible for IFN-γ release by Streptococcus salivarius, a Gram-positive commensal, previously noted to possess potent interleukin-12 (IL-12)-inducing potential.

A defined serum-free medium useful for monitoring anti-melanoma responses induced by dendritic cell immunotherapy.

Animal sera provide a non-defined source of nutrients and growth factors for mammalian cell culture. Animal serum supplementation may also introduce experimental artefacts, including immune responses against foreign serum proteins. This artefact is particularly apparent in tumour immunotherapy experiments using dendritic cells (DC) and melanoma cells cultured in fetal calf serum (FCS)-replete media.