Intranasal coadministration of Cholera toxin with amoeba lysates modulates the secretion of IgA and IgG antibodies, production of cytokines and expression of pIgR in the nasal cavity of mice in the model of Naegleria fowleri meningoencephalitis

Exp Parasitol. 2014 Nov:145 Suppl:S84-92. doi: 10.1016/j.exppara.2014.04.002. Epub 2014 Apr 13.

Abstract

The nasal mucosa is the first contact with antigens to induce IgA response. The role of this site has rarely been studied. We have shown than intranasal administration with Naegleria fowleri lysates plus Cholera toxin (CT) increased the protection (survival up to 100%) against N. fowleri infection in mice and apparently antibodies IgA and IgG together with polymorphonuclear (PMN) cells avoid the attachment of N. fowleri to apical side of the nasal epithelium. We also observed that nasal immunization resulted in the induction of antigen-specific IgG subclasses (IgG1 and IgG2a) in nasal washes at days 3 and 9 after the challenge and IgA and IgG in the nasal cavity, compared to healthy and infected mice. We found that immunization with both treatments, N. fowleri lysates plus CT or CT alone, increased the expression of the genes for alpha chain, its receptor (pIgR), and it also increased the expression of the corresponding proteins evidenced by the ∼65 and ∼74kDa bands, respectively. Since the production of pIgR, IgA and IgG antibodies, is up-regulated by some factors, we analyzed the expression of genes for IL-10, IL-6, IFN-γ, TNF-α and IL-1β by using RT-PCR of nasal passages. Immunization resulted in an increased expression of IL-10, IL-6, and IFN-γ cytokines. We also aimed to examine the possible influences of immunization and challenge on the production of inflammatory cytokines (TNF-α and IL-1β). We observed that the stimulus of immunization inhibits the production of TNF-α compared to the infected group where the infection without immunization causes an increase in it. Thus, it is possible that the coexistence of selected cytokines produced by our immunization model may provide a highly effective immunological environment for the production of IgA, IgG and pIgR as well as a strong activation of the PMN in mucosal effector tissue such as nasal passages.

Keywords: Cholera toxin; Cytokines; Naegleria fowleri; Nasal passages; Polymeric Ig receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Blotting, Western
  • Cholera Toxin / administration & dosage*
  • Cholera Toxin / immunology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation
  • Goats
  • Immunoglobulin A / genetics
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Immunoglobulin Isotypes / genetics
  • Immunoglobulin Isotypes / metabolism*
  • Immunohistochemistry
  • Mice
  • Naegleria fowleri / chemistry*
  • Naegleria fowleri / immunology
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / parasitology
  • RNA, Messenger / metabolism
  • Rabbits
  • Real-Time Polymerase Chain Reaction
  • Receptors, Polymeric Immunoglobulin / genetics
  • Receptors, Polymeric Immunoglobulin / metabolism*

Substances

  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • RNA, Messenger
  • Receptors, Polymeric Immunoglobulin
  • Cholera Toxin