Is the thymus a target organ in infectious diseases?

Abstract

The thymus is a central lymphoid organ, in which T cell precursors differentiate and generate most of the so-called T cell repertoire. Along with a variety of acute infectious diseases, we and others determined important changes in both microenvironmental and lymphoid compartments of the organ. For example, one major and common feature observed in acute viral, bacterial and parasitic diseases, is a depletion of cortical thymocytes, mostly those bearing the CD4-CD8 double positive phenotype. This occurs simultaneously to the relative enrichment in medullary CD4 or CD8 single positive cells, expressing high densities of the CD3 complex. Additionally we noticed a variety of changes in the thymic microenvironment (and particularly its epithelial component), comprising abnormal location of thymic epithelial cell subsets as well has a denser Ia-bearing cellular network. Moreover, the extracellular matrix network was altered with an intralobular increase of basement membrane proteins that positively correlated with the degree of thymocyte death. Lastly, anti-thymic cell antibodies were detected in both human and animal models of infectious diseases, and in some of them a phenomenon of molecular mimicry could be evidenced. Taken together, the data reviewed herein clearly show that the thymus should be regarded as a target in infectious diseases.

Low dose aerosol infection of mice with virulent type A Francisella tularensis induces severe thymus atrophy and CD4+CD8+ thymocyte depletion

“…Deletion of thymocytes thereby eliminates the precursors of the cells that would otherwise help to maintain effective immunity against the pathogen. Besides the phenotypic changes identified in the present study, thymocytes may be also functionally affected (such as cytokine production and cell cycling) [5,12]. In this regard, although the thymus is not the site of memory cell generation and is probably not essential for the maintenance of memory cell pool, thymus destruction will nevertheless have the potential impact on the lymphocyte output and/or functional lymphocyte responses to foreign antigens.…”

“…Many pathogens and their products have previously been shown to affect thymus development (reviewed in [5]). Several mechanisms have been implicated in the process of thymocyte death and thymus atrophy during the course of an infection.…”

“…Several mechanisms have been implicated in the process of thymocyte death and thymus atrophy during the course of an infection. While some pathogens can interact directly with thymocytes and thymic epithelial cells, others cause cortical depletion of the thymus in an indirect way, mediated either by the secretion of adrenal glucocorticosteroid hormones resulting from the acute stress of the infection or by pathogen-induced release of certain cytokines [5].…”

“…One of the common features occurring in acute natural infections in humans and experimental animals is a thymus atrophy defined by loss of thymus weight and cellularity (reviewed in [5]). In this regard, experimental infection of mice with a number of bacteria (Listeria monocytogenes [6], Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae [7]), viruses (murine cytomegalovirus [8], murine leukemia virus [9], HIV [10], and mouse hepatitis virus [11]), and protozoa (Toxoplasma gondii [12], and Trypanosoma cruzi) induces a severe lymphocytopaenia and marked thymus atrophy and loss of cortical lymphocytes.…”

Differential expression of notch signaling-related transcripts accompanies Pro-thymocyte proliferation and phenotype transition induced by epidermal growth factor plus insulin in fetal thymus organ cultures

“…As a target organ in infectious diseases, it displays a plastic behavior, its regression in response to infectious or stressing agents being followed, as soon as these stimuli are discontinued, by a prompt reconstitution that in many aspects mimics ontogeny (Savino et al 1992). The organ development involves an ordered sequence of bi-directional signaling events between two cellular compartments, a complex microenvironment that eventually turns permissive to seeding by pluripotent hematopoietic precursors, and the progeny of the last (Anderson 2000).…”