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Infectious Agents and Bone Marrow Failure: A Causal or a Casual Connection? - PubMed

  • ️Fri Jan 01 2021

Infectious Agents and Bone Marrow Failure: A Causal or a Casual Connection?

Valentina Giudice et al. Front Med (Lausanne). 2021.

Abstract

Acquired bone marrow failure (BMF) syndromes are considered immune-mediated disorders because hematological recovery after immunosuppressive therapies is the strongest indirect evidence of the involvement of immune cells in marrow failure development. Among pathophysiology hypotheses, immune derangement after chronic antigen exposure or cross-reactivity between viral particles and cellular components are the most accepted; however, epitopes against whom these lymphocytes are directed to remain unknown. In this study, we showed that BMF-associated immunodominant clones, namely the most represented T cells carrying an antigen-specific T-cell receptor (TCR) sequence in a random pool, were frequently associated with those described in various infectious diseases, such as cytomegalovirus (CMV) and Mycobacterium tuberculosis infection. We hypothesize that these pathogens might elicit an autoimmune response triggered by cross-reactivity between pathogen-related components and proteins or might be expanded as an unspecific response to a global immune dysregulation during BMF. However, those frequent intracellular pathogens might not only be passengers in marrow failure development, while playing a central role in starting the autoimmune response against hematopoietic stem cells.

Keywords: TCR repertoire; bone marrow failure; bone marrow failure syndrome; immune response; infectious diseases.

Copyright © 2021 Giudice, Risitano and Selleri.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1

Pathogen involvement in bone marrow failure (BMF). Primary viral or mycobacterial infection occurs in the lower pulmonary system where pathogens infect alveolar cells and macrophages (Mφ), or where Mφ phagocyte mycobacteria containing the infection. Subsequently, Mφ migrate to pulmonary lymph nodes and presents antigens (Ag) to dendritic cells that processed and present Ag to naïve T cells. Once primed, naïve T cells differentiate primarily in T helper (Th) 1 cells releasing pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), interferon-gamma (IFNγ), or interleukins (IL) that, together with type I interferons (IFNs), trigger the activation of effector cytotoxic CD8+ T cells (CTLs). After activation, CTLs directly kill infected cells, and pathogen particles and cellular components are released and likely captured by dendritic cells, processed, and presented as novel antigens. On the other hand, pathogen particles might induce a cross-reactivity with cellular components and start an autoimmune response that might be sustained by Th17 cells and Th17-related cytokines (IL-17 or IL-22). The figure was created in

Biorender.com

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