Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune responses

Abstract

Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect vector to humans by exposure of mucosal surfaces to infected insect excreta. We have used an oral challenge murine model that mimics vector-borne transmission to study T. cruzi mucosal infection. Although gastric secretions have microbicidal activity against most infectious pathogens, we demonstrate that T. cruzi can invade and replicate in the gastric mucosal epithelium. In addition, gastric mucosal invasion appears to be the unique portal of entry for systemic T. cruzi infection after oral challenge. The mucosal immune responses stimulated by T. cruzi gastric infection are protective against a secondary mucosal parasite challenge. This protective mucosal immunity is associated with increased numbers of lymphocytes that secrete parasite-specific immunoglobulin A. Our results document the first example of systemic microbial invasion through gastric mucosa and suggest the feasibility of a mucosal vaccine designed to prevent infection with this important human pathogen.

Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

“…The primary site of parasite entry in oral infection is still unknown. Previous data proved that in orally infected mice, parasites are not detected within the oropharynx and esophagus, instead, amastigote nests are present in the stomach [ 23 ]. In line with these findings, another group suggested that parasite glycoproteins, such as gp82 and gp30, are involved in gastric invasion following intragastric/intrapharyngeal inoculation [ 27 , 37 , 42 , 43 ].…”

“…These models of oral T . cruzi infections result in parasitemia and heart parasitism, which indicates systemic infection [ 22 , 23 , 24 , 25 , 26 ]. In addition, T .…”

“…This initial invasion is related to the establishment of a progressive gastritis and allowing further systemic dissemination of the parasite. Nonetheless, the short replication period at this mucosal site induces specific immunity, as protection was observed after a secondary mucosal challenge, involving the production of IgA and IgG antibodies [ 23 ]. Interestingly, humoral and cellular responses are also protective after parasite inoculation in the conjunctival mucosa, a natural portal of entry for T .…”

“…In orally infected mice, inflammatory infiltrates are observed in several tissues, such as the pancreas, spleen, liver, bone marrow, heart, duodenum, adrenal glands, brain and skeletal muscle [ 23 ]. Moreover, it was suggested that intraepithelial and lamina propria lymphocytes are involved in IFN-γ, but not IL-4 production, in orally infected hosts [ 23 ]. Interestingly, this infection route does not affect CD8 + T cell response [ 26 ].…”

Trypanosoma cruzi Transmission Cycle Among Wild and Domestic Mammals in Three Areas of Orally Transmitted Chagas Disease Outbreaks

“…31,32 In addition, it was recently observed that the gastric juice improves the infective potential of the parasite. 33,34 Indeed, infection by the oral route may better explain infection of predators (top of food webs) rather than skin contamination with infected feces of triatomines in the often dense animal fur. This is also probably the case with primitive hunting communities that were recognized consumers of raw meat 35 and probably were not very concerned about washing hands or foodstuffs.…”