AOKI MARIA DEL PILAR
Congresos y reuniones científicas
Título:
Modulation of purinergic signaling has a tissue-dependent impact on the immune response against Trypanosoma cruzi infection
Autor/es:
EBERHARDT, N; SANMARCO, LM; GARCÍA, MC; PONCE, NE; THEUMER, M; AOKI, MP
Reunión:
Congreso; Reunión conjunta de Sociedades de Biociencias; 2017
Resumen:
Adenosine (ADO), an immune-regulatory metabolite, is produced
by hydrolysis of ATP that accumulates during tissue injury and inflammation. ADO generated through CD73 activity is an extracellular
signaling molecule that is involved in anti-inflammatory mechanisms
and provides a feedback to control tissue damage mediated by the
host immune response to several infections. We hypothesize that
the balance between ATP and ADO is crucial in the development of
Chagas disease. The aim of this study was to determine the balance
of purinergic signals and its impact in the host immune response
developed in different T. cruzitarget tissues. The kinetic of cardiac
macrophage (Ma) subsets showed a predominant inflammatory/M1
profile throughout the acute infection (p<0.001) with higher frequency of IL-12+ and iNOS+ M1 Ma (p<0.05) and augmented cardiac NO
levels (p<0.001) in CD73-deficient (KO) compared to C57BL/6 (WT)
mice. Moreover, KO mice exhibited increased frequency of cardiac IFN-γ+ and CD107a+ CD8 T lymphocytes (p<0.05) and a consequent lower cardiac parasite load (p<0.05). Nevertheless, these
mice had higher parasitemia (p<0.05) associated to lower plasmatic
NO levels. Strikingly, in visceral adipose tissue (VAT), parasite load
was increased (p<0.01) in KO mice, this may be due to an increased
basal VAT/body weight ratio (p<0.001) compared to uninfected WT
mice, generating an important niche for parasite growth. As in VAT,
parasite load in KO liver was augmented compared to WT (p<0.05).
Furthermore, CD73 abrogation significantly decreased extracellular
release of ADO in infected heart and VAT but not in liver. These findings could be explained by the different purinergic signaling impact
in the target tissues evidenced by about 12-fold increase in ATP/
ADO ratio in KO/WT heart compared to a 5 and 1 in VAT and liver
respectively. In conclusion, purinergic system differentially modulates the host immune response against T. cruziinfection in a target
tissue-dependent manner
by hydrolysis of ATP that accumulates during tissue injury and inflammation. ADO generated through CD73 activity is an extracellular
signaling molecule that is involved in anti-inflammatory mechanisms
and provides a feedback to control tissue damage mediated by the
host immune response to several infections. We hypothesize that
the balance between ATP and ADO is crucial in the development of
Chagas disease. The aim of this study was to determine the balance
of purinergic signals and its impact in the host immune response
developed in different T. cruzitarget tissues. The kinetic of cardiac
macrophage (Ma) subsets showed a predominant inflammatory/M1
profile throughout the acute infection (p<0.001) with higher frequency of IL-12+ and iNOS+ M1 Ma (p<0.05) and augmented cardiac NO
levels (p<0.001) in CD73-deficient (KO) compared to C57BL/6 (WT)
mice. Moreover, KO mice exhibited increased frequency of cardiac IFN-γ+ and CD107a+ CD8 T lymphocytes (p<0.05) and a consequent lower cardiac parasite load (p<0.05). Nevertheless, these
mice had higher parasitemia (p<0.05) associated to lower plasmatic
NO levels. Strikingly, in visceral adipose tissue (VAT), parasite load
was increased (p<0.01) in KO mice, this may be due to an increased
basal VAT/body weight ratio (p<0.001) compared to uninfected WT
mice, generating an important niche for parasite growth. As in VAT,
parasite load in KO liver was augmented compared to WT (p<0.05).
Furthermore, CD73 abrogation significantly decreased extracellular
release of ADO in infected heart and VAT but not in liver. These findings could be explained by the different purinergic signaling impact
in the target tissues evidenced by about 12-fold increase in ATP/
ADO ratio in KO/WT heart compared to a 5 and 1 in VAT and liver
respectively. In conclusion, purinergic system differentially modulates the host immune response against T. cruziinfection in a target
tissue-dependent manner
