Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion.
Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM). This parasite invades its host by penetrating the olfactory mucosa. During the initial stages of infection, the host response is initiated by the secretion of mucus that traps the trophozoites. Despite this response, some trophozoites are able to reach, adhere to and penetrate the epithelium. In the present work, we evaluated the effect of mucins on amoebic adherence and cytotoxicity to Madin-Darby canine kidney (MDCK) cells and the MUC5AC-inducing cell line NCI-H292. We showed that mucins inhibited the adhesion of amoebae to both cell lines; however, this inhibition was overcome in a time-dependent manner. N. fowleri re-established the capacity to adhere faster than N. gruberi. Moreover, mucins reduced the cytotoxicity to target cells and the progression of the illness in mice. In addition, we demonstrated mucinolytic activity in both Naegleria strains and identified a 37 kDa protein with mucinolytic activity. The activity of this protein was inhibited by cysteine protease inhibitors. Based on these results, we suggest that mucus, including its major mucin component, may act as an effective protective barrier that prevents most cases of PAM; however, when the number of amoebae is sufficient to overwhelm the innate immune response, the parasites may evade the mucus by degrading mucins via a proteolytic mechanism.
Cervantes-Sandoval
Isaac
I
Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Av. Manuel M. Carpio and Plan de Ayala, Mexico City 11340, Mexico.|Department of Experimental Pathology, Center for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN 2508, Mexico City 07360, Mexico.
Serrano-Luna
José de Jesús
JJ
Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN 2508, Mexico City 07360, Mexico.
García-Latorre
Ethel
E
Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Av. Manuel M. Carpio and Plan de Ayala, Mexico City 11340, Mexico.
Tsutsumi
Víctor
V
Department of Experimental Pathology, Center for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN 2508, Mexico City 07360, Mexico.
Shibayama
Mineko
M
Department of Experimental Pathology, Center for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN 2508, Mexico City 07360, Mexico.
D000562:Amebiasis / Q000276:immunology* / Q000469:parasitology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000378:metabolism; D009077:Mucins / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D016848:Naegleria fowleri / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D011133:Polysaccharide-Lyases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism
D055271:Mucin 5AC; D009077:Mucins; D015800:Protozoan Proteins; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase