Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

Abstract

The skin is an organ harboring several types of immune cells that participate in innate and adaptive immune responses. The immune system of the skin comprises both skin cells and professional immune cells that together constitute what is designated skin-associated lymphoid tissue (SALT). In this review, I extensively discuss the organization of SALT and the mechanisms involved in its responses to infectious diseases of the skin and mucosa. The nature of these SALT responses, and the cellular mediators involved, often determines the clinical course of such infections. I list and describe the components of innate immunity, such as the roles of the keratinocyte barrier and of inflammatory and natural killer cells. I also examine the mechanisms involved in adaptive immune responses, with emphasis on new cytokine profiles, and the role of cell death phenomena in host-pathogen interactions and control of the immune responses to infectious agents. Finally, I highlight the importance of studying SALT in order to better understand host-pathogen relationships involving the skin and detail future directions in the immunological investigation of this organ, especially in light of recent findings regarding the skin immune system.

Keywords: cytokines; immune response; infections; innate immunity; keratinocytes; lymphocytes; skin.

FIG 1

Schematic representation of the distribution of immune cells that form the skin-associated lymphoid tissue (SALT) in the epidermis and dermis of the skin.

FIG 2

Schematic representation of the components of the inflammasome and its role in the production of proinflammatory cytokines. NLRP inflammasome activation can be induced by cytosolic PAMPs and DAMPs, leading to IL-1β and IL-18 activation. Activation of caspase-1 by the inflammasome may also induce pyropitosis.

FIG 3

Phenotypic subpopulations of macrophages and their differentiation based on the specific profile of cytokines and chemokines. Each subpopulation is involved in specific physiological and pathological processes and the expression of a particular profile of cytokines, enzymes, and metalloproteinases, which may contribute to microbicidal, regenerative, and atherosclerotic plaques.

FIG 4

Diversity in helper T lymphocyte profiles, their differentiation factors, and characteristic cytokine profiles.

FIG 5

Integrated view of the association between the host cells and infectious agents in the context of the skin’s in situ immune response. Note that the triggered mechanisms culminate in the activation of professional and nonprofessional immune cells, such as keratinocytes, which can, however, interfere with the immune response cascade against various harmful agents. These cells act as a mechanical barrier and can interfere with the immune response in the skin. Endothelial activation is required for the migration of immune cells from the blood to the tissue.