TY - JOUR
T1 - Secrets and lies of host-microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases
AU - Ria, Francesco
AU - Delogu, Giovanni
AU - Ingrosso, L.
AU - Sali, Michela
AU - Di Sante, G.
AU - Di Sante, Gabriele
PY - 2024
Y1 - 2024
N2 - Here we critically discuss data supporting the view that microbial agents (pathogens, pathobionts or commensals alike) play a relevant role in the pathogenesis of multifactorial diseases, but their role is concealed by the rules presiding over T cell antigen recognition and trafficking. These rules make it difficult to associate univocally infectious agents to diseases' pathogenesis using the paradigm developed for canonical infectious diseases. (Cross-)recognition of a variable repertoire of epitopes leads to the possibility that distinct infectious agents can determine the same disease(s). There can be the need for sequential infection/colonization by two or more microorganisms to develop a given disease. Altered spreading of infectious agents can determine an unwanted activation of T cells towards a pro-inflammatory and trafficking phenotype, due to differences in the local microenvironment. Finally, trans-regulation of T cell trafficking allows infectious agents unrelated to the specificity of T cell to modify their homing to target organs, thereby driving flares of disease. The relevant role of microbial agents in largely prevalent diseases provides a conceptual basis for the evaluation of more specific therapeutic approaches, targeted to prevent (vaccine) or cure (antibiotics and/or Biologic Response Modifiers) multifactorial diseases.
AB - Here we critically discuss data supporting the view that microbial agents (pathogens, pathobionts or commensals alike) play a relevant role in the pathogenesis of multifactorial diseases, but their role is concealed by the rules presiding over T cell antigen recognition and trafficking. These rules make it difficult to associate univocally infectious agents to diseases' pathogenesis using the paradigm developed for canonical infectious diseases. (Cross-)recognition of a variable repertoire of epitopes leads to the possibility that distinct infectious agents can determine the same disease(s). There can be the need for sequential infection/colonization by two or more microorganisms to develop a given disease. Altered spreading of infectious agents can determine an unwanted activation of T cells towards a pro-inflammatory and trafficking phenotype, due to differences in the local microenvironment. Finally, trans-regulation of T cell trafficking allows infectious agents unrelated to the specificity of T cell to modify their homing to target organs, thereby driving flares of disease. The relevant role of microbial agents in largely prevalent diseases provides a conceptual basis for the evaluation of more specific therapeutic approaches, targeted to prevent (vaccine) or cure (antibiotics and/or Biologic Response Modifiers) multifactorial diseases.
KW - Environment-related balance of health/disease
KW - Germ-related autoimmune disorders
KW - Immune cell trafficking
KW - Micorbial agents in multifactorial disease
KW - Microbial-Immune balance
KW - Environment-related balance of health/disease
KW - Germ-related autoimmune disorders
KW - Immune cell trafficking
KW - Micorbial agents in multifactorial disease
KW - Microbial-Immune balance
UR - http://hdl.handle.net/10807/273375
U2 - 10.1007/s00018-023-05040-y
DO - 10.1007/s00018-023-05040-y
M3 - Article
SN - 1420-9071
VL - 81
SP - N/A-N/A
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
ER -