Infectious Diseases and the Lymphoid Extracellular Matrix Remodeling: A Focus on Conduit System

Abstract

The conduit system was described in lymphoid organs as a tubular and reticular set of structures compounded by collagen, laminin, perlecan, and heparin sulfate proteoglycan wrapped by reticular fibroblasts. This tubular system is capable of rapidly transport small molecules such as viruses, antigens, chemokines, cytokines, and immunoglobulins through lymphoid organs. This structure plays an important role in guiding the cells to their particular niches, therefore participating in cell cooperation, antigen presentation, and cellular activation. The remodeling of conduits has been described in chronic inflammation and infectious diseases to improve the transport of antigens to specific T and B cells in lymphoid tissue. However, malnutrition and infectious agents may induce extracellular matrix remodeling directly or indirectly, leading to the microarchitecture disorganization of secondary lymphoid organs and their conduit system. In this process, the fibers and cells that compound the conduit system may also be altered, which affects the development of a specific immune response. This review aims to discuss the extracellular matrix remodeling during infectious diseases with an emphasis on the alterations of molecules from the conduit system, which damages the cellular and molecular transit in secondary lymphoid organs compromising the immune response.

Keywords: conduit system; extracellular matrix; infectious diseases; lymph node; remodeling; spleen.

Figure 1

Illustrative scheme of conduit channel. The conduit system is responsible for driving, selectively, proteins, chemokines, and cytokines through the interaction between proteins and proteins associated with collagen fiber into the conduit lumen. Fibrillin molecules maintain the collagen fibers bound between each other and the basal membrane. The conduit lumen is wrapped by an amorphous substance that is secreted by the fibroblast reticular cells. The amorphous substance is composed of laminin, heparan sulfate, nidogen, perlecan, fibrillin, and other proteins of basal proteins. The scheme is based on conduit transverse.

Figure 2

Detection of fibroblast reticular cells in the spleen of chronically infected dogs with Leishmania infantum by immunohistochemistry. (A) Infected and asymptomatic dog. (B) Infected and symptomatic dog. In this figure, the spleen of the symptomatic dog shows fewer fibroblast reticular cells than the asymptomatic dog. Fibroblast reticular cells are represented in red color in the figure.

Figure 3

Illustrative scheme of the splenic microenvironment. (A) Organized spleen: In this illustration, it is possible to visualize an organized splenic with pulp and splenic compartmentalization such as germinal center and lymphatic periarteriolar sheath, marginal zone and capsule to exert its physiological role. As represented, the extracellular matrix maintains its normal composition. (B) Disorganized spleen: Illustrative scheme of a chronically inflamed microenvironment of spleen tissue. During chronic inflammation, the extracellular matrix undergoes remodeling favoring the entry of new inflammatory cells. In persistent inflammation, the extracellular matrix loses its remodeling control showing an increase of cytokines such as Tumour Necrosis Factor-α (TNF-α) and Transforming Growth Factor-β (TGF-β) together with high production of matrix metallopeptidases and microbicidal molecules such as Reactive Nitrogen Species (RNS), Reactive Oxygen Species (ROS), and lysosomal enzymes. These events lead to tissue damage by breaking or accumulating some structural proteins like laminin and collagen. In this situation, a cell reduction and the white pulp atrophy are commonly observed.

Figure 4

Flowchart showing briefly the steps of extracellular matrix remodeling and changes in lymphoid tissue during acute and chronic infectious processes.