Identification and characterization of a novel population of murine colonic Sca-1+ cells and implications in Chagas disease.
disease, a chronic degenerative condition caused by the protozoan parasite Trypanosoma
cruzi, infects an estimated 10 million people worldwide, mostly in Latin America where
it is endemic. The disease has two phases, acute and chronic. Although acute infection
is characterized by a high parasite burden in the blood and other tissues, parasitism is
kept in check by innate and ... read moreadaptive immunity. However, heavy tissue parasitism coupled
with a strong immune response elicits tissue destruction, especially in the heart,
colon, and esophagus. Nevertheless, most patients progress from acute infection to the
chronic phase without permanent tissue damage or sequela, except for less than 5%, who
succumb to fulminating myocarditis and encephalomyelitis. Patients acutely infected with
T cruzi progress to the chronic indeterminate phase, characterized by extremely low
tissue parasitism and absence of symptoms and tissue damage. After many years or
decades, about 30% of patients in the indeterminate phase progress to life-threatening
pathology in the heart (cardiomegaly) and 10% in the gastrointestinal tract
(megaesophagus and megacolon). The time course of Chagas disease progression led us to
hypothesize that T cruzi helps the host repair infected tissues by expressing factors
such as Parasite Derived Neurotropic Factor (PDNF) that act in concert with endogenous
host repair mechanisms. Much attention has been given to the emerging concept that adult
stem cells help tissue repair by paracrine signaling, such as through upregulating
expression of anti-inflammatory cytokines and growth factors. In support of our
hypothesis, recent results in our lab demonstrate that PDNF stimulates self-renewal and
survival of reparative Sca-1+ cardiac progenitor/stem cells (CPCs), and enhances
secretion of the anti-inflammatory cytokine TSG-6. However, the heart is by no means the
sole organ in Chagas disease to suffer severe insult, and given that specific
tissue-resident stem cells are being identified throughout the body, it stands to reason
that a similar population of progenitor/stem cell exists in the colon with similar
reparative properties. My project seeks to isolate a novel population of Sca-1+ cells in
the colon of naïve mice, characterize the morphology and surface markers, and
profile cellular interactions with T cruzi.
Thesis (M.S.)--Tufts University, 2016.
Submitted to the Dept. of Immunology.
Advisor: Mercio Perrin.
Committee: Honorine Ward, Pilar Alcaide, and Thereza Imanishi-Kari.
Keyword: Immunology.read less