Dendritic Cell Involvement in Pulmonary Granuloma Formation Elicited by Bacillus Calmette-Guérin in Rats

Abstract

Dendritic cells (DCs) are the most potent antigen-presenting cells that play a central role in initiating the primary immune response. However, their role in granulomatous inflammation has not been well studied. The aim of the present study was to elucidate the role of DCs in granuloma formation. Using a rat model of bacillus Calmette-Guérin (BCG)-elicited pulmonary granulomas, we investigated the distribution of DCs in the granulomas by immunohistochemistry with a rat-DC-specific monoclonal antibody, OX62. We found numerous large, pleiomorphic OX62(+) cells accumulating at the borders of the pulmonary granulomas. The OX62(+) cells isolated from the granulomatous lung showed intense surface expression of major histocompatibility complex class II, B7-1, and B7-2, and a lack of T cell- and monocyte/macrophage-specific markers. Their ultrastructural morphology was characteristic of DCs. Functionally, they had potent capacity to stimulate allogeneic T cells as well as purified protein derivative-specific syngeneic T cells in the absence of exogenous peptides. Based on these findings, the OX62(+) cells infiltrating the granulomas were considered to be DCs expressing BCG-derived peptides. These results indicate that DCs contribute to pulmonary granuloma formation elicited by BCG by means of their potent antigen-presenting function, providing a novel insight into DC function in T cell-mediated granulomatous immune responses.

Differentiation, Maturation, and Survival of Dendritic Cells by Osteopontin Regulation

“…They are essential for the containment of infections that induce cellular immune responses (12,27,33,36). We recently reported that DCs play a key role in the initiation of cell-mediated immune granuloma formation (12).…”

“…Thus, DCs play a crucial role during the initiation and regulation of immune responses. Recently, we and others reported that DCs are essential for granuloma formation against bacterial antigens in animal models (12,33,36).…”

“…Thus, DCs play a crucial role during the initiation and regulation of immune responses. Recently, we and others reported that DCs are essential for granuloma formation against bacterial antigens in animal models (12,33,36).Osteopontin (OPN), also known as early T-lymphocyte activation-1 (Eta-1), is a phosphoprotein that contains arginineglycine-aspartate (RGD). Although OPN is classified as an extracellular matrix (ECM) protein, OPN has only recently been shown to be an important component of early cellular immune responses (18).…”

Inverse Correlation of Maturity and Antibacterial Activity in Human Dendritic Cells

“…A major human pathogen predominantly infecting its host by the aerosolic route is Mycobacterium tuberculosis (M. Tb), the causative agent of tuberculosis. Recent work demonstrated that mycobacteria-infected DC accumulate in the spleens of M. Tb-infected mice (4) and are detectable in granulomas of infected rats (5) and humans (3,6). In vitro experiments revealed that M. Tb is phagocytosed by human DC (7), mainly by the interaction between the mycobacterial lipoarabinomannan and DC-specific ICAM-1-grabbing nonintegrin (DC-SIGN) (3,8).…”

A Regulatory Effect of the Balance between TNF-α and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice

“…The recruited T lymphocytes release cytokines that further activate the macrophages and drive epithelioid cell differentiation, eventually resulting in granuloma formation (10 -12). Recent studies showed that functionally mature dendritic cells (DCs), which possess potent Ag-presenting function and can activate T lymphocytes, participate in the granulomatous reaction (13)(14)(15). However, an excessive granulomatous response results in tissue injury and fails to localize infection (16).…”