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Effects of CD4+CD25+Foxp3+regulatory T cells on early Plasmodium yoelii 17XL infection in BALB/c mice

Published online by Cambridge University Press:  02 July 2009

GUANG CHEN ,
JUN LIU ,
QING-HUI WANG ,
YI WU ,
HUI FENG ,
WEI ZHENG ,
SHENG-YU GUO ,
DONG-MEI LI ,
JI-CHUN WANG  and
YA-MING CAO
GUANG CHEN
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China Department of Parasitology, College of Basic Medical Sciences, Jamusi University, Jamusi 154000, China
JUN LIU
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China
QING-HUI WANG
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China
YI WU
Affiliation:
Department of Internal Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China
HUI FENG
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China
WEI ZHENG
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China
SHENG-YU GUO
Affiliation:
Department of Rheumatology and Immunology, Second Clinical College, China Medical University, No.36 Sanhao Street, Heping District, Shenyang, China, 110004
DONG-MEI LI
Affiliation:
Shanghai Institute of Biological Products, 1262YanAn Road (W), Shanghai 200000, China
JI-CHUN WANG
Affiliation:
Department of Pathogenic Biology, College of Basic Medical Sciences, China Medical University, No. 92 Beier Road, Heping District, Shenyang, China
YA-MING CAO*
Affiliation:
Department of Immunology, College of Basic Medical Sciences, China Medical University, No.92 Beier Road, Heping District, Shenyang, China
*
*Corresponding author: Department of Immunology, College of Basic Medical Sciences, China Medical University, No. 92 Beier Road, Heping District, Shenyang, China. Tel: +86 24 23256666 5346. Fax: +86 24 23264417. E-mail address: ymcao@mail.cmu.edu.cn
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Summary

The outcome of Plasmodium yoelii 17XL-infected BALB/c and DBA/2 mice, ranging from death to spontaneous cure, respectively, depends largely on the establishment of effective pro-inflammatory type 1 responses during the early stages of infection and associates with CD4+CD25+Foxp3+regulatory T cells (Tregs). Here, effects of Tregs were analysed on early P. yoelii 17XL infection in BALB/c and DBA/2 mice. In vivo depletion of Tregs significantly reversed the inhibited establishment of effective pro-inflammatory type 1 responses in BALB/c mice, indicating that this cell population contributed to the suppression of T-cell function in malaria. Moreover, the proportion and absolute numbers of IL-10-secreting Tregs in BALB/c mice were significantly higher than that found in DBA/2 mice by intracytoplasmic staining, and IL-10 production was correlated with the Tregs population. In addition, in vivo Tregs depletion decreased the production of IL-10 and the apoptosis of CD4+ T cells. Consistently, IL-10R blockade also had the same effect as that of Tregs depletion in P. yoelii 17XL-infected BALB/c mice. Our data demonstrate that Tregs perhaps have an important role in regulating pro-inflammatory type 1 responses in an IL-10-dependent manner and induce CD4+ T cell apoptosis during the early stage of P. yoelii 17XL infection.

Keywords

CD4+CD25+Foxp3+regulatory T cellsPlasmodium yoelii 17XLearly infection
Type
Research Article
Information
Parasitology , Volume 136 , Issue 10 , September 2009 , pp. 1107 - 1120
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Anderson, C. F., Mendez, S. and Sacks, D. L. (2005). Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57 BL/6 mice. Journal of Immunology 174, 2934–2941.Google Scholar
Asseman, C., Mauze, S., Leach, M. W., Coffman, R. L. and Powrie, F. (1999). An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. The Journal of Experimental Medicine 190, 995–1004.CrossRefGoogle ScholarPubMed
Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. and Sacks, D. L. (2002). CD4+CD25+regulatory T cells control Leishmania major persistence and immunity. Nature, London 420, 502–507.CrossRefGoogle ScholarPubMed
Brustoski, K., Moller, U., Kramer, M., Hartgers, F. C., Kremsner, P. G., Krzych, U. and Luty, A. J. (2006). Reduced cord blood immune effector-cell responsiveness mediated by CD4+ cells induced in utero as a consequence of placental Plasmodium falciparum infection. The Journal of Infectious Diseases 193, 146–154.CrossRefGoogle ScholarPubMed
Cambos, M., Bélanger, B., Jacques, A., Roulet, A. and Scorza, T. (2008). Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion. International Journal for Parasitology 38, 229–238.CrossRefGoogle Scholar
CDC-US. Centers for Disease Control and Prevention (n.d.) Chapter 4. Available: http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx.Google Scholar
Collins, W. E., Jeffery, G. M. and Roberts, J. M. (2004). A retrospective examination of reinfection of humans with Plasmodium vivax. The American Journal of Tropical Medicine and Hygiene 70, 642–644. [PubMed: 15211006]Google Scholar
Couper, K. N., Blount, D. G. and Riley, E. M. (2008). IL-10: the master regulator of immunity to infection. Journal of Immunology 180, 5771–5777.Google Scholar
Couper, K. N., Blount, D. G., de Souza, J. B., Suffia, I., Belkaid, Y. and Riley, E. M. (2007). Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice. Journal of Immunology 178, 4136–4146. [PubMed: 17371969]CrossRefGoogle ScholarPubMed
Couper, K. N., Phillips, R. S., Brombacher, F. and Alexander, J. (2005). Parasite-specific IgM plays a significant role in the protective immune response to asexual erythrocytic stage Plasmodium chabaudi AS infection. Parasite Immunology 27, 171–180.CrossRefGoogle Scholar
Goudy, K. S., Burkhardt, B. R., Wasserfall, C., Song, S., Campbell-Thompson, M. L., Brusko, T., Powers, M. A., Clare-Salzler, M. J., Sobel, E. S., Ellis, T. M., Flotte, T. R. and Atkinson, M. A. (2003). Systemic overexpression of IL-10 induces CD4+CD25+cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion. Journal of Immunology 171, 2270–2278.CrossRefGoogle Scholar
Greenwood, B. M., Bradley-Moore, A. M., Bryceson, A. D. and Palit, A. (1972). Immunosuppression in children with malaria. Lancet 1, 169–172.Google Scholar
Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S. and Noelle, R. J. (2005). Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. Journal of Immunology 174, 1783–1786.Google Scholar
Hisaeda, H., Maekawa, Y., Iwakawa, D., Okada, H., Himeno, K., Kishihara, K., Tsukumo, S. and Yasutomo, K. (2004). Escape of malaria parasites from host immunity requires CD4+CD25+regulatory T cells. Nature Medicine 10, 29–30.CrossRefGoogle ScholarPubMed
Hori, S. and Sakaguchi, S. (2004). Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes and Infection 6, 745–751.CrossRefGoogle ScholarPubMed
Jacobs, P., Radzioch, D. and Stevenson, M. M. (1995). Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice. Journal of Immunology 155, 5306–5313.CrossRefGoogle Scholar
Korbel, D. S., Finney, O. C. and Riley, E. M. (2004). Natural killer cells and innate immunity to protozoan pathogens. International Journal for Parasitology 34, 1517–1528.CrossRefGoogle ScholarPubMed
Lee, K. S., Sen, G., Snapper, C. M., Lee, K. S., Sen, G. and Snapper, C. M. (2005). Endogenous CD4+CD25+regulatory T cells play no apparent role in the acute humeral response to intact Streptococcus pneumoniae. Infection and Immunity 73, 4427–4431.CrossRefGoogle Scholar
Long, T. T., Nakazawa, S., Onizuka, S., Huaman, M. C. and Kanbara, H. (2003). Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice. International Journal for Parasitology 33, 175–183.CrossRefGoogle ScholarPubMed
Martin, B., Banz, A., Bienvenu, B., Cordier, C., Dautigny, N., Bécourt, C. and Lucas, B. (2004). Suppression of CD4+T lymphocyte effector functions by CD4+CD25+cells in vivo. Journal of Immunology 172, 3391–3398.Google Scholar
Ma, S. H., Zheng, L., Liu, Y. J., Guo, S. Y., Feng, H., Chen, G., Li, D. M., Wang, J. C. and Cao, Y. M. (2007). Plasmodium yoelii: influence of antimalarial treatment on acquisition of immunity in BALB/c and DBA/2 mice. Experimental Parasitology 116, 266–272.CrossRefGoogle ScholarPubMed
Nakamura, K., Kitani, A. and Strober, W. (2001). Cell contact-dependent immune-suppression by CD4+CD25+regulatory T cells is mediated by cell surface-bound transforming growth factor beta. The Journal of Experimental Medicine 194, 629–644.Google Scholar
Nie, C. Q., Bernard, N. J., Schofield, L. and Hansen, D. S. (2007). CD4+CD25+regulatory T cells suppress CD4+T-cell function and inhibit the development of Plasmodium berghei-specific TH1 responses involved in cerebral malaria pathogenesis. Infection and Immunity 75, 2275–2282.CrossRefGoogle ScholarPubMed
Omer, F. M., de Souza, J. B. and Riley, E. M. (2003). Differential induction of TGF-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. Journal of Immunology 171, 5430–5436.Google Scholar
Riley, E. M., Wahl, S., Perkins, D. J. and Schofield, L. (2006). Regulating immunity to malaria. Parasite Immunology 28, 35–49.Google Scholar
Rouse, B. T. and Suvas, S. (2004). Regulatory cells and infectious agents: detentes cordiale and contraire, Journal of Immunology 173, 2211–2215.CrossRefGoogle ScholarPubMed
Roland, J., Soulard, V., Sellier, C., Drapier, A. M., Di Santo, J. P., Cazenave, P. A. and Pied, S. (2006). NK cell responses to Plasmodium infection and control of intrahepatic parasite development. Journal of Immunology 177, 1229–1239.CrossRefGoogle ScholarPubMed
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor a-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology 155, 1151–1164.Google Scholar
Seixas, E. and Ostler, D. (2005). Plasmodium chabaudi chabaudi (AS): differential cellular responses to infection in resistant and susceptible mice. Experimental Parasitology 110, 394–405.Google Scholar
Stevenson, M. M., Tam, M. F., Wolf, S. F. and Sher, A. (1995). IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. Journal of Immunology 155, 2545–2556.CrossRefGoogle Scholar
Shevach, E. M. (2002). CD4+CD25+ suppressor T cells: more questions than answers. Nature Reviews. Immunology 2, 389–400.CrossRefGoogle ScholarPubMed
Snow, R. W., Guerra, C. A., Noor, A. M., Myint, H. and Hay, S. I. (2005). The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, London 434, 214–217.Google Scholar
Taylor-Robinson, A. W. and Phillips, R. S. (1994). B cells are required for the switch from Th1 to Th2 regulated immune responses to Plasmodium chabaudi infection. Infection and Immunity 62, 2490–2498.Google Scholar
Thornton, M. A. and Shevach, E. M. (1998). CD4+CD25+immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting Interleukin 2 production. The Journal of Experimental Medicine 188, 287–296.CrossRefGoogle ScholarPubMed
Urban, B. C., Ing, R. and Stevenson, M. M. (2005). Early interactions between blood-stage Plasmodium parasites and the immune system. Current Topics in Microbiology and Immunology 297, 25–70.Google Scholar
Wipasa, J., Xu, H., Stowers, A. and Good, M. F. (2001). Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection. Journal of Immunology 167, 3903–3909.CrossRefGoogle ScholarPubMed
Wu, Y., Wang, Q. H., Zheng, L., Feng, H., Liu, J., Ma, S. H. and Cao, Y. M. (2007). Plasmodium yoelii: distinct CD4+CD25+regulatory T cell responses during the early stages of infection in susceptible and resistant mice. Experimental Parasitology 115, 301–304.Google Scholar
Yazdani, S. S., Mukherjee, P., Chauhan, V. S. and Chitnis, C. E. (2006). Immune responses to asexual blood-stages of malaria parasites. Current Molecular Medicine 6, 187–203.Google Scholar