The underlying molecular mechanisms for multi-walled carbon nanotube (MWCNT)-induced
in vivo
toxicity on innate immunity are still largely unclear. Considering the potential of
Caenorhabditis elegans
for the study of innate immune response of animals, we employed this
in vivo
assay system to investigate
the e
ff
ects of MWCNTs on innate immune response of animals and the underlying mechanisms. Pre-
exposure to MWCNTs at concentrations more than 100
μ
gL
−
1
enhanced the adverse e
ff
ect of fungal
infection in reducing lifespan. With regard to the underlying cellular mechanisms, we found that MWCNT
pre-exposure enhanced colony formation of
Candida albicans
in the body of nematodes, and suppressed
innate immun... More
The underlying molecular mechanisms for multi-walled carbon nanotube (MWCNT)-induced
in vivo
toxicity on innate immunity are still largely unclear. Considering the potential of
Caenorhabditis elegans
for the study of innate immune response of animals, we employed this
in vivo
assay system to investigate
the e
ff
ects of MWCNTs on innate immune response of animals and the underlying mechanisms. Pre-
exposure to MWCNTs at concentrations more than 100
μ
gL
−
1
enhanced the adverse e
ff
ect of fungal
infection in reducing lifespan. With regard to the underlying cellular mechanisms, we found that MWCNT
pre-exposure enhanced colony formation of
Candida albicans
in the body of nematodes, and suppressed
innate immune response of nematodes by decreasing expression levels of some antimicrobial genes. With
regard to the underlying molecular mechanisms, we found that MWCNTs decreased expression levels of
pmk
-
1
,
sek
-
1
, and
nsy
-
1
genes encoding the p38 mitogen activated protein kinase (MAPK) signaling
pathway, and inhibited translational expression of PMK-1::GFP in the intestine and phosphorylation of
PMK-1. Epistasis assays showed that MWCNTs required the involvement of the p38 MAPK signaling
pathway mediated by a NSY-1-SEK-1-PMK-1 cascade to enhance the toxicity of fungal infection, increase
fungal colony formation, and suppress innate immune response. Thus, our results suggest that MWCNTs
may possess immunoinhibitory e
ff
ects by a
ff
ecting the functions of the p38 MAPK signaling pathway. Our
study also provides meaningful insights into the role of innate immune system of hosts against the toxicity
of environmental toxicants.