PMID- 18660993
OWN - NLM
STAT- MEDLINE
DCOM- 20081224
LR  - 20190606
IS  - 1678-8060 (Electronic)
IS  - 0074-0276 (Linking)
VI  - 103
IP  - 4
DP  - 2008 Jun
TI  - TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and 
      promotes heart tissue damage during Trypanosoma cruzi infection: beneficial 
      effects of TNF-alpha blockade.
PG  - 375-85
LID - S0074-02762008000400011 [pii]
AB  - In Chagas disease, understanding how the immune response controls parasite growth 
      but also leads to heart damage may provide insight into the design of new 
      therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for 
      resistance to acute Trypanosoma cruzi infection; however, in patients suffering 
      from chronic T. cruzi infection, plasma TNF-alpha levels correlate with 
      cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis 
      formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of 
      TNF-alpha, especially signaling through the receptor TNFR1/p55, to the 
      pathophysiology of T. cruzi infection was evaluated with a focus on the 
      development of myocarditis and heart dysfunction. Colombian strain-infected 
      C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-alpha+ splenocytes. 
      Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite 
      burden, they succumbed to acute infection. Similar to C57BL/6 mice, 
      Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, 
      reduced CD8-enriched myocarditis was associated with defective activation of 
      CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-alpha treatment 
      reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though 
      parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and 
      anti-TNF-alpha-treated infected mice showed regular expression of connexin-43 and 
      reduced fibronectin deposition, respectively. Furthermore, anti-TNF-alpha 
      treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our 
      results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis 
      formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as 
      a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.
FAU - Kroll-Palhares, Karina
AU  - Kroll-Palhares K
AD  - Laboratorio de Auto-Imunidade e Imuno-Regulacao, Instituto Oswaldo Cruz-Fiocruz, 
      Rio de Janeiro, Brasil.
FAU - Silverio, Jaline Coutinho
AU  - Silverio JC
FAU - Silva, Andrea Alice da
AU  - Silva AA
FAU - Michailowsky, Vladimir
AU  - Michailowsky V
FAU - Marino, Ana Paula
AU  - Marino AP
FAU - Silva, Neide Maria
AU  - Silva NM
FAU - Carvalho, Cristiano Marcelo Espinola
AU  - Carvalho CM
FAU - Pinto, Luzia Maria de Oliveira
AU  - Pinto LM
FAU - Gazzinelli, Ricardo Tostes
AU  - Gazzinelli RT
FAU - Lannes-Vieira, Joseli
AU  - Lannes-Vieira J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Brazil
TA  - Mem Inst Oswaldo Cruz
JT  - Memorias do Instituto Oswaldo Cruz
JID - 7502619
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antibodies, Monoclonal/*pharmacology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Movement
MH  - Chagas Cardiomyopathy/drug therapy/*immunology
MH  - Chronic Disease
MH  - Female
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Infliximab
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, CCR5/*immunology
MH  - Receptors, Tumor Necrosis Factor, Type I/*antagonists & 
      inhibitors/blood/immunology
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/blood/immunology
EDAT- 2008/07/29 09:00
MHDA- 2008/12/25 09:00
CRDT- 2008/07/29 09:00
PHST- 2008/03/17 00:00 [received]
PHST- 2008/06/09 00:00 [accepted]
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2008/12/25 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
AID - S0074-02762008000400011 [pii]
AID - 10.1590/s0074-02762008000400011 [doi]
PST - ppublish
SO  - Mem Inst Oswaldo Cruz. 2008 Jun;103(4):375-85. doi: 
      10.1590/s0074-02762008000400011.