Intranasal immunization with Naegleria fowleri lysates and Cry1Ac induces metaplasia in the olfactory epithelium and increases IgA secretion

Abstract

According to previous reports, intranasal administration of the Cry1Ac protein alone or with amoebic lysates increases protection against Naegleria fowleri meningoencephalitis in mice, apparently by eliciting IgA responses in the nasal mucosa. In the current study, we performed an immunohistochemical analysis of IgA in the nasal mucosa of mice immunized intranasally with Cry1Ac, and amoebic lysates or a combination of both. The animals were sacrificed 24 h after the last immunization or after an intranasal lethal challenge with N. fowleri. Our results indicate that all of the intranasal immunizations provoked an increase in areas with metaplasia in the olfactory epithelium, allowing for secretion of IgA. As a result, IgA antibodies were found interacting with trophozoites in the nasal lumen, and there was a marked increase of IgA in the metaplasic epithelium. On the other hand in nonimmunized mice trophozoites were observed invading the nasal mucosa, which was not the case for immunized mice. Our results suggest that intranasal immunization provokes cellular changes in the olfactory epithelium, leading to greater protection against N. fowleri that is probably caused by an increased secretion of IgA. The increased IgA response induced in the nasal mucosa by immunization probably impedes both amoebic adhesion and subsequent invasion of the parasite to the nasal epithelium.

An overview of the safety and biological effects of Bacillus thuringiensis Cry toxins in mammals

“…In contrast, when Cry1Ac was co-administered intranasally as adjuvant with Naegleria fowleri lysates, only this treatment induced metaplasia in the olfactory epithelium and increased IgA secretion compared to immunization with lysates alone, effects that may be related to the increased protection conferred by this treatment; however, this result deserves further analysis ( Jarillo-Luna et al, 2008). Because when this protein is intranasally administered to mice, it is able to induce an increased proportion of activated T and B lymphocytes and an increased proportion of T lymphocytes producing cytokines and significant specific IgA and IgG antibody cell responses in nasal lymphocytes isolated from both nasal-associated lymphoid tissue (NALT) and nasal passages (NP) (Rodriguez-Monroy and Moreno-Fierros, 2010).…”

Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review

“…In another study, it was determined that combined administration of Bacillus thuringiensis Cry1Ac protoxin and N. fowleri lysate provided the prolonged survival in mice compared to the mice only receiving N. fowleri lysate. Both mucosal IgG and IgA production enhanced, and the level of IgG remained high even after 2 months of inoculation and in the nasal lumen, IgA interaction with trophozoites was also reported on comparing to the non‐immunized animal where trophozoites penetrated into the nasal mucosa . Molecular based study revealed that Cry1Ac as an adjuvant administered along with amoebal lysate in STAT6+/+ mice has a 100% survival rate on comparison with STAT6−/− mice who did not survive on introducing intranasal N. fowleri .…”

Neutrophils extracellular traps damage Naegleria fowleri trophozoites opsonized with human IgG

“…To date, we still do not know the precise mechanism by which neutrophils could be eliminating N. fowleri trophozoites. We have suggested that one of the main defence mechanism of the nasal mucosa against N. fowleri in previously immunized mice is the trophozoites phagocytosis by polymorphonuclear cells through their receptors at the Fc fraction of antibodies . However, there are many factors involved in neutrophil interaction with the microorganisms to avoid pathogen colonization.…”