TY - JOUR
T1 - Mycobacterium manresensis induces trained immunity in vitro
AU - Rodriguez-Cortes, Alheli
AU - Segalés Coma, Joaquim
AU - Cardona, Pere-Joan
AU - de Homdedeu, Miquel
AU - Sanchez-Moral, Lidia
AU - Violán, Concepció
AU - Ràfols, Neus
AU - Ouchi, Dan
AU - Martín, Berta
AU - Peinado, Miguel A.
AU - Arch Sisquella, Marta
AU - Perez-Zsolt, Daniel
AU - Muñoz-Basagoiti, Jordana
AU - Izquierdo Useros, Nuria
AU - Salvador, Betlem
AU - Matllo, Joan
AU - López-Serrano, Sergi
AU - Torán-Montserrat, Pere
AU - Morros, Rosa
AU - Monfà, Ramon
AU - Sarrias, Maria-Rosa
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/6/16
Y1 - 2023/6/16
N2 - The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.
AB - The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.
KW - Biological sciences
KW - Immunology
KW - Microbiology
KW - Molecular biology
UR - http://www.scopus.com/inward/record.url?scp=85160420592&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106873
DO - 10.1016/j.isci.2023.106873
M3 - Article
C2 - 37250788
SN - 2589-0042
VL - 26
SP - 106873
EP - 106873
JO - iScience
JF - iScience
IS - 6
M1 - 106873
ER -
