MGL1 Receptor Plays a Key Role in the Control of T. cruzi Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-kappa B and NLRP3 Pathways
Por:
Rodriguez, Tonathiu, Pacheco-Fernandez, Thalia, Vazquez-Mendoza, Alicia, Nieto-Yanez, Oscar, Juarez-Avelar, Imelda, Reyes, Jose L., Terrazas, Luis I., Rodriguez-Sosa, Miriam
Publicada:
1 ene 2020
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
Macrophage galactose-C type lectin (MGL)1 receptor is involved in the
recognition of Trypanosoma cruzi (T. cruzi) parasites and is important
for the modulation of the innate and adaptive immune responses. However,
the mechanism by which MGL1 promotes resistance to T. cruzi remains
unclear. Here, we show that MGL1 knockout macrophages (MGL1(-/-) M phi)
infected in vitro with T. cruzi were heavily parasitized and showed
decreased levels of reactive oxygen species (ROS), nitric oxide (NO),
IL-12 and TNF-alpha compared to wild-type macrophages (WT M phi).
MGL1(-/-) M phi stimulated in vitro with T. cruzi antigen (TcAg) showed
low expression of TLR-2, TLR-4 and MHC-II, which resulted in deficient
splenic cell activation compared with similar co-cultured WT M phi.
Importantly, the activation of p-ERK1/2, p-c-Jun and p-NF-kappa B p65
were significantly reduced in MGL1(-/-) M phi exposed to TcAg.
Similarly, procaspase 1, caspase 1 and NLRP3 inflammasome also displayed
a reduced expression that was associated with low IL-beta production.
Our data reveal a previously unappreciated role for MGL1 in M phi
activation through the modulation of ERK1/2, c-Jun, NF-kappa B and NLRP3
signaling pathways, and to the development of protective innate immunity
against experimental T. cruzi infection.
Filiaciones:
Rodriguez, Tonathiu:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
Pacheco-Fernandez, Thalia:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
Vazquez-Mendoza, Alicia:
UNAM, FES Iztacala, Carrera Optometria, Tlalnepantla 54090, Estado Mexico, Mexico
Nieto-Yanez, Oscar:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
Juarez-Avelar, Imelda:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
Reyes, Jose L.:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
Terrazas, Luis I.:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
UNAM, FES Iztacala, Lab Nacl Salud, Tlalnepantla 54090, Estado Mexico, Mexico
Rodriguez-Sosa, Miriam:
UNAM, FES Iztacala, Unidad Biomed UBIMED, Tlalnepantla 54090, Estado Mexico, Mexico
|