Sinusoidal immunity: macrophages at the lymphohematopoietic interface

Macrophages are widely distributed throughout the body, performing vital homeostatic and defense functions after local and systemic perturbation within tissues. In concert with closely related dendritic cells and other myeloid and lymphoid cells, which mediate the innate and adaptive immune response, macrophages determine the outcome of the inflammatory and repair processes that accompany sterile and infectious injury and microbial invasion. This article will describe and compare the role of specialized macrophage populations at two critical interfaces between the resident host lymphohematopoietic system and circulating blood and lymph, the carriers of cells, humoral components, microorganisms, and their products. Sinusoidal macrophages in the marginal zone of the spleen and subcapsular sinus and medulla of secondary lymph nodes contribute to the innate and adaptive responses of the host in health and disease. Although historically recognized as major constituents of the reticuloendothelial system, it has only recently become apparent that these specialized macrophages in close proximity to B and T lymphocytes play an indispensable role in recognition and responses to exogenous and endogenous ligands, thus shaping the nature and quality of immunity and inflammation. We review current understanding of these macrophages and identify gaps in our knowledge for further investigation.