Oral Exposure to Trypanosoma cruzi Elicits a Systemic CD8+ T Cell Response and Protection against Heterotopic Challenge

被引:28
作者
Collins, Matthew H.
Craft, Julie M.
Bustamante, Juan M.
Tarleton, Rick L.
机构
[1] Univ Georgia, Dept Cellular Biol, Athens, GA 30502 USA
[2] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30502 USA
关键词
TYPE-1 IMMUNITY PROVIDES; CHAGAS-DISEASE CONTROL; IN-VIVO; INTRAMUSCULAR VACCINATION; INTESTINAL EPITHELIUM; PARASITIC INFECTIONS; MUCOSAL IMMUNITY; DENDRITIC CELLS; B-CELL; TRANSMISSION;
D O I
10.1128/IAI.01080-10
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Trypanosoma cruzi infects millions of people in Latin America and often leads to the development of Chagas disease. T. cruzi infection can be acquired at or near the bite site of the triatomine vector, but per os infection is also a well-documented mode of transmission, as evidenced by recent microepidemics of acute Chagas disease attributed to the consumption of parasite-contaminated foods and liquids. It would also be convenient to deliver vaccines for T. cruzi by the oral route, particularly live parasite vaccines intended for the immunization of reservoir hosts. For these reasons, we were interested in better understanding immunity to T. cruzi following oral infection or oral vaccination, knowing that the route of infection and site of antigen encounter can have substantial effects on the ensuing immune response. Here, we show that the route of infection does not alter the ability of T. cruzi to establish infection in muscle tissue nor does it impair the generation of a robust CD8(+) T cell response. Importantly, oral vaccination with attenuated parasites provides protection against wild-type (WT) T. cruzi challenge. These results strongly support the development of whole-organism-based vaccines targeting reservoir species as a means to alleviate the burden of Chagas disease in affected regions.
引用
收藏
页码:3397 / 3406
页数:10
相关论文
共 68 条
[1]   Quantitative imaging of Plasmodium transmission from mosquito to mammal [J].
Amino, R ;
Thiberge, S ;
Martin, B ;
Celli, S ;
Shorte, S ;
Frischknecht, F ;
Ménard, R .
NATURE MEDICINE, 2006, 12 (02) :220-224
[2]   The Trypanosoma cruzi proteome [J].
Atwood, JA ;
Weatherly, DB ;
Minning, TA ;
Bundy, B ;
Cavola, C ;
Opperdoes, FR ;
Orlando, R ;
Tarleton, RL .
SCIENCE, 2005, 309 (5733) :473-476
[3]   Mechanisms of leucocyte recruitment to the inflamed large intestine: redundancy in integrin and addressin usage [J].
Bell, L. V. ;
Else, K. J. .
PARASITE IMMUNOLOGY, 2008, 30 (03) :163-170
[4]  
Belyakov IM, 2009, J IMMUNOL, V182, P1779, DOI 10.4049/jimmunol.0990002
[5]   The importance of local mucosal HIV-specific CD8+ cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12 [J].
Belyakov, IM ;
Ahlers, JD ;
Brandwein, BY ;
Earl, P ;
Kelsall, BL ;
Moss, B ;
Strober, W ;
Berzofsky, JA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (12) :2072-2081
[6]   Localization of lectin-binding sites on the surface of Trypanosoma cruzi grown in chemically defined conditions [J].
Bourguignon, SC ;
de Souza, W ;
Souto-Padrón, T .
HISTOCHEMISTRY AND CELL BIOLOGY, 1998, 110 (05) :527-534
[7]   Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease [J].
Bustamante, Juan M. ;
Bixby, Lisa M. ;
Tarleton, Rick L. .
NATURE MEDICINE, 2008, 14 (05) :542-550
[8]   Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs [J].
Calzascia, T ;
Masson, F ;
Di Berardino-Besson, W ;
Contassot, E ;
Wilmotte, R ;
Aurrand-Lions, M ;
Rüegg, C ;
Dietrich, PY ;
Walker, PR .
IMMUNITY, 2005, 22 (02) :175-184
[9]   In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds [J].
Canavaci, Adriana M. C. ;
Bustamante, Juan M. ;
Padilla, Angel M. ;
Perez Brandan, Cecilia M. ;
Simpson, Laura J. ;
Xu, Dan ;
Boehlke, Courtney L. ;
Tarleton, Rick L. .
PLOS NEGLECTED TROPICAL DISEASES, 2010, 4 (07)
[10]   Prime-boost immunization with cruzipain co-administered with MALP-2 triggers a protective immune response able to decrease parasite burden and tissue injury in an experimental Tryponosoma cruzi infection model [J].
Cazorla, Silvia I. ;
Frank, Fernanda M. ;
Becker, Pablo D. ;
Corral, Ricardo S. ;
Guzman, Carlos A. ;
Malchiodi, Emilio L. .
VACCINE, 2008, 26 (16) :1999-2009