Folia Parasitologica, vol. 63 (2016)

Folia Parasitologica 63:010 (2016) | DOI: 10.14411/fp.2016.010

Bacillus Calmette-Guérin-inoculation at different time points influences the outcome of C57BL/6 mice infected with Plasmodium chabaudi chabaudi AS

Dong-Hua Cao1,2, Ji-Chun Wang3, Jun Liu1, Yun-Ting Du1, Li-Wang Cui4, Ya-Ming Cao1
1 Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China;
2 Aristogenesis Center, Hospital of People's Liberation Army, Shenyang, China;
3 Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China;
4 Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA

Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium tuberculosis vaccine. We performed a series of co-infection experiments with BCG-Plasmodium chabaudi chabaudi Landau, 1965 AS using C57BL/6 mice to analyse whether BCG can affect the development of protective immunity to infection with Plasmodium spp. and the mechanism of this protection. We divided mice into four groups: BCG-inoculation 4 weeks prior to P. c. chabaudi AS infection (B-4w-Pc); simultaneous BCG-inoculation and P. c. chabaudi AS infection (Pc+B); BCG-inoculation 3 days post P. c. chabaudi AS (Pc-3-B) infection; and mono-P. c. chabaudi AS infection as control (Pc). The parasitemia level in the B-4w-Pc group was noticeably higher than control group at 6-19 days post infection (dpi). Compared with the control group, the proportion of CD4+CD69+ T cells was significantly reduced 5, 8 and 12 dpi, but the proportion of CD4+CD25+Foxp3+ Tregs was significantly increased in the B-4w-Pc group on 5 and 8 dpi. The B-4w-Pc group also demonstrated reduced levels of IFN-γ and TNF-α on 5 and 8 dpi and significantly elevated level of IL-10 on 12 dpi. There were significantly fewer mDCs (CD11c+CD11b+) and pDCs (CD11c+B220+) in the B-4w-Pc group than the control group at all the time points post infection and the expression of MHC II was noticeably reduced on day 8 pi. Our findings confirmed that BCG inoculation prior to Plasmodium infection resulted in excessive activation and proliferation of Tregs and upregulation of anti-inflammatory mediators, which inhibited establishment of a Th1-dominant immune response during the early stages of Plasmodium infection by inhibiting dendritive cells response. BCG inoculation prior to P. c. chabaudi AS infection may contribute to overgrowth of parasites as well as mortality in mice.

Keywords: murine malarial parasite, BCG, co-infection, protective immunity

Received: October 10, 2015; Accepted: March 3, 2016; Published online: April 1, 2016


References

  1. Artavanis-Tsakonas K., Tongren J.E., Riley E.M. 2003: The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clin. Exp. Immunol. 133: 145-152. Go to original source... Go to PubMed...
  2. Banchereau J., Steinman R.M. 1998: Dendritic cells and the control of immunity. Nature 392: 245-252. Go to original source... Go to PubMed...
  3. Barclay V.C., Sim D., Chan B.H., Nell L.A., Rabaa M.A., Bell A.S., Anders R.F., Read A.F. 2012: The evolutionary consequences of blood-stage vaccination on the rodent malaria Plasmodium chabaudi. PLoS Biol. 10: e1001368. Go to original source... Go to PubMed...
  4. Bueno L.L., Morais C.G., Araújo F.F., Gomes J.A., Corrêa-Oliveira R., Soares I.S., Lacerda M.V., Fujiwara R.T., Braga E.M. 2010: Plasmodium vivax: induction of CD4+CD25+FoxP3+ regulatory T cells during infection are directly associated with level of circulating parasites. PLoS ONE 5: e9623. Go to original source... Go to PubMed...
  5. Cameron A., Reece S.E., Drew D.R., Haydon D.T., Yates A.J. 2013: Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi: environmental and genetic effects. Evol. Appl. 6: 365-376. Go to original source... Go to PubMed...
  6. Chen G., Liu J., Wang Q.H., Wu Y., Feng H., Zheng W., Guo S.Y., Li D.M., Wang J.C., Cao Y.M. 2009: Effects of CD4(+)CD25(+)Foxp3(+) regulatory T cells on early Plasmodium yoelii 17XL infection in BALB/c mice. Parasitology 136: 1107-1120. Go to original source... Go to PubMed...
  7. Clark I.A., Allison A.C., Cox F.E. 1976: Protection of mice against Babesia and Plasmodium with BCG. Nature 259: 309-311. Go to original source... Go to PubMed...
  8. Clark I.A., Virelizier J.L., Carswell E.A., Wood P.R. 1981: Possible importance of macrophage-derived mediators in acute malaria. Infect. Immun. 32: 1058-1066. Go to PubMed...
  9. Couper K.N., Phillips R.S., Brombacher F., Alexander J. 2005: Parasite-specific IgM plays a significant role in the protective immune response to asexual erythrocytic stage Plasmodium chabaudi AS infection. Parasite Immunol. 27: 171-180. Go to original source... Go to PubMed...
  10. Cox J., Semoff S., Hommel M. 1987: Plasmodium chabaudi: a rodent malaria model for in vivo and in vitro cytoadherence of malaria parasites in the absence of knobs. Parasite Immunol. 9: 543-561. Go to original source... Go to PubMed...
  11. Diao J., Winter E., Chen W., Cantin C., Cattral M.S. 2004: Characterization of distinct conventional and plamacytoid dendritic cell-committed precursors in murine bone marrow. J. Immunol. 173: 1826-1833. Go to original source... Go to PubMed...
  12. Feng H., Zhu X.T., Qi Z.M., Wang Q.H., Wang G.G., Pan Y.Y., Li Y., Zheng L., Jiang Y.J., Shang H., Cui L., Cao Y.M. 2012: Transient attenuated Foxp3 expression on CD4⁺ T cells treated with 7D4 mAb contributes to the control of parasite burden in DBA/2 mice infected with lethal Plasmodium chabaudi chabaudi AS. Scand. J. Immunol. 75: 46-53. Go to original source... Go to PubMed...
  13. Flynn J.L., Chan J., Triebold K.J., Dalton D.K., Stewart T.A., Bloom B.R. 1993: An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178: 2249-2254. Go to original source... Go to PubMed...
  14. Gilks C.F., Walliker D., Newbold C.I. 1990: Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi - a rodent malaria model. Parasite Immunol. 12: 45-64. Go to original source... Go to PubMed...
  15. Haidaris C.G., Haynes J.D., Meltzer M.S., Allison A.C. 1983: Serum containing tumor necrosis factor is cytotoxic for the human malaria parasite Plasmodium falciparum. Infect. Immun. 42: 385-393. Go to PubMed...
  16. Ing R., Stevenson M.M. 2009: Dendritic cell and NK cell reciprocal cross talk promotes gamma interferon-dependent immunity to blood-stage Plasmodium chabaudi AS infection in mice. Infect. Immun. 77: 770-782. Go to original source... Go to PubMed...
  17. Jangpatarapongsa K., Chootong P., Sattabongkot J., Chotivanich K., Sirichaisinthop J., Tungpradabkul S., Hisaeda H., Troye-Blomberg M., Cui L., Udomsangpetch R. 2008: Plasmodium vivax parasites alter the balance of myeloid and plasmacytoid dendritic cells and the induction of regulatory T cells. Eur. J. Immunol. 38: 2697-2705.  Go to original source... Go to PubMed...
  18. Keane J., Gershon S., Wise R.P., Mirabile-Levens E., Kasznica J., Schwieterman W.D., Siegel J.N., Braun M.M. 2001: Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N. Engl. J. Med. 345: 1098-1104. Go to original source... Go to PubMed...
  19. Langhorne J., Gillard S., Simon B., Slade S., Eichmann K. 1989: Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int. Immunol. 1: 416-424. Go to original source... Go to PubMed...
  20. Langhorne J., Quin S.J., Sanni L.A. 2002: Mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. Chem. Immunol. 80: 204-228. Go to original source... Go to PubMed...
  21. Leisewitz A.L., Rockett K., Kwiatkowski D. 2008: BCG-malaria co-infection has paradoxical effects on C57BL/6 and A/J mouse strains. Parasite Immunol. 30: 1-12. Go to original source... Go to PubMed...
  22. Liu Y.J. 2001: Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106: 259-262. Go to original source... Go to PubMed...
  23. Mackinnon M.J., Walker P.R., Rowe J.A. 2002: Plasmodium chabaudi: rosetting in a rodent malaria model. Exp. Parasitol. 101: 121-128. Go to original source... Go to PubMed...
  24. Malhotra I., Mungai P., Muchiri E., Ouma J., Sharma S., Kazura J.W., King C.L. 2005: Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. Infect. Immun. 73: 3462-3470. Go to original source... Go to PubMed...
  25. Matsumoto S., Yukitake H., Kanbara H., Yamada H., Kitamura A., Yamada T. 2000: Mycobacterium bovis bacillus Calmette-Guérin induces protective immunity against infection by Plasmodium yoelii at blood-stage depending on shifting immunity toward Th1 type and inducing protective IgG2a after the parasite infection. Vaccine 19: 779-787. Go to original source... Go to PubMed...
  26. Murphy J.R. 1981: Host defenses in murine malaria: nonspecific resistance to Plasmodium berghei generated in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation. Infect. Immun. 33: 199-211. Go to PubMed...
  27. Page K.R., Jedlicka A.E., Fakheri B., Noland G.S., Kesavan A.K., Scott A.L., Kumar N., Manabe Y.C. 2005: Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific. Infect. Immun. 73: 8369-8380. Go to original source... Go to PubMed...
  28. Range N., Magnussen P., Mugomela A., Malenganisho W., Changalucha J., Temu M.M., Mngara J., Krarup H., Friis H., Andersen A.B. 2007: HIV and parasitic co-infections in tuberculosis patients: a cross-sectional study in Mwanza, Tanzania. Ann. Trop. Med. Parasitol. 101: 343-351. Go to original source... Go to PubMed...
  29. Roche P.A., Furuta K. 2015: The ins and outs of MHC class II-mediated antigen processing and presentation. Nat. Rev. Immunol. 15: 203-216. Go to original source... Go to PubMed...
  30. Sam H., Stevenson M.M. 1999: In vivo IL-12 production and IL-12 receptors β1 and β2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria. J Immunol. 162: 1582-1589. Go to PubMed...
  31. Schneider P., Bell A.S., Sim D.G., O'Donnell A.J., Blanford S., Paaijmans K.P., Read A.F., Reece S.E. 2012: Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi. Proc. Biol. Sci. 279: 4677-4685. Go to original source... Go to PubMed...
  32. Seixas E., Ostler D. 2005: Plasmodium chabaudi chabaudi (AS): differential cellular responses to infection in resistant and susceptible mice. Exp. Parasitol. 110: 394-405. Go to original source... Go to PubMed...
  33. Song X., Liang F., Liu N., Luo Y., Xue H., Yuan F., Tan L., Sun Y, Xi C., Xi Y. 2009: Construction and characterization of a novel DNA vaccine that is potent antigen-specific tolerizing therapy for experimental arthritis by increasing CD4(+)CD25(+)Treg cells and inducing Th1 to Th2 shift in both cells and cytokines. Vaccine 27: 690-700. Go to original source... Go to PubMed...
  34. Spence P.J., Jarra W., Lévy P., Nahrendorf W., Langhorne J. 2012: Mosquito transmission of the rodent malaria parasite Plasmodium chabaudi. Malar. J. 11: 407. Go to original source... Go to PubMed...
  35. Stevenson M., Lemieux S., Skamene E. 1984: Genetic control of resistance to murine malaria. J. Cell. Biochem. 24: 91-102. Go to original source... Go to PubMed...
  36. Stevenson M.M., Huang D.Y., Podoba J.E., Nowotarski M.E. 1992: Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL/6 and susceptible A/J mice. Infect. Immun. 60: 1193-1201. Go to PubMed...
  37. Stevenson M.M., Riley E.M. 2004: Innate immunity to malaria. Nat. Rev. Immunol. 4: 169-180. Go to original source... Go to PubMed...
  38. Stevenson M.M., Tam M.F. 1993: Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin. Exp. Immunol. 92: 77-83. Go to original source... Go to PubMed...
  39. Stevenson M.M., Tam M.F., Belosevic M., van der Meide P.H., Podoba J.E. 1990: Role of endogenous γ interferon in host response to infection with blood-stage Plasmodium chabaudi AS. Infect. Immun. 58: 3225-3232. Go to PubMed...
  40. Stevenson M.M., Tam M.F., Wolf S.F., Sher A. 1995: IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-γ and TNF-α and occurs via a nitric oxide-dependent mechanism. J. Immunol. 155: 2545-2556. Go to PubMed...
  41. Stevenson M.M., Urban B.C. 2006: Antigen presentation and dendritic cell biology in malaria. Parasite Immunol. 28: 5-14. Go to original source... Go to PubMed...
  42. Taverne J., Bate C.A., Playfair J.H. 1989: Induction of TNF in vitro as a model for the identification of toxic malaria antigens. Lymphokine Res. 8: 317-322. Go to PubMed...
  43. Taverne J., Depledge P., Playfair J.H. 1982: Differential sensitivity in vivo of lethal and nonlethal malarial parasites to endotoxin-induced serum factor. Infect. Immun. 37: 927-934. Go to PubMed...
  44. Taverne J., Dockrell H.M., Playfair J.H. 1981: Endotoxin-induced serum factor kills malarial parasites in vitro. Infect. Immun. 33: 83-89. Go to PubMed...
  45. Taylor-Robinson A.W., Phillips R.S. 1994: B cells are required for the switch from Th1 to Th2 regulated immune responses to Plasmodium chabaudi infection. Infect. Immun. 62: 2490-2498. Go to PubMed...
  46. Taylor-Robinson A.W., Phillips R.S., Severn A., Moncada S., Liew F.Y. 1993: The role of TH1 and TH2 cells in a rodent malaria infection. Science 260: 1931-1934. Go to original source... Go to PubMed...
  47. Thapa R., Mallick D., Biswas B. 2010: Perinatal malaria and tuberculosis co-infection: a case report. Int. J. Infect. Dis. 14: e254-6. Go to original source... Go to PubMed...
  48. Waisberg M., Lin C.K., Huang C.Y., Pena M., Orandle M., Bolland S., Pierce S.K. 2013: The impact of genetic susceptibility to systemic lupus erythematosus on placental malaria in mice. PLoS ONE 8: e62820. Go to original source... Go to PubMed...
  49. Wang G.G., Chen G., Feng H., Liu J., Jiang Y.J., Shang H., Cao Y.M. 2013: Plasmodium chabaudi AS: distinct CD4(+)CD25(+)Foxp3(+) regulatory T cell responses during infection in DBA/2 and BALB/c mice. Parasitol. Int. 62: 24-31. Go to original source... Go to PubMed...
  50. Wang Q.H., Liu Y.J., Liu J., Chen G., Zheng W., Wang J.C., Cao Y.M. 2009: Plasmodium yoelii: assessment of production and role of nitric oxide during the early stages of infection in susceptible and resistant mice. Exp. Parasitol. 121: 268-273. Go to original source... Go to PubMed...
  51. World Health Organization 2014: Global Tuberculosis Report 2014. WHO Press, Geneva, 7 pp.
  52. World Health Organization 2015: World Malaria Report 2015. WHO Press, Geneva, 40 pp.
  53. Wozencraft A.O., Dockrell H.M., Taverne J., Targett G.A., Playfair J.H. 1984: Killing of human malaria parasites by macrophage secretory products. Infect. Immun. 43: 664-669. Go to PubMed...
  54. Wu J.J., Chen G., Liu J., Wang T., Zheng W., Cao Y.M. 2010: Natural regulatory T cells mediate the development of cerebral malaria by modifying the pro-inflammatory response. Parasitol. Int. 59: 232-241. Go to original source... Go to PubMed...
  55. Wu Y., Wang Q.H., Zheng L., Feng H., Liu J., Ma S.H., Cao Y.M. 2007: Plasmodium yoelii: distinct CD4(+)CD25(+) regulatory T cell responses during the early stages of infection in susceptible and resistant mice. Exp. Parasitol. 115: 301-304. Go to original source... Go to PubMed...
  56. Wykes M.N., Liu X.Q., Beattie L., Stanisic D.I., Stacey K.J., Smyth M.J., Thomas R., Good M.F. 2007: Plasmodium strain determines dendritic cell function essential for survival from malaria. PLoS Pathog. 3: e96. Go to original source... Go to PubMed...
  57. Yazdani S.S., Mukherjee P., Chauhan V.S., Chitnis C.E. 2006: Immune responses to asexual blood-stages of malaria parasites. Curr. Mol. Med. 6: 187-203. Go to original source... Go to PubMed...
  58. Zheng W., Wang Q.H., Feng H., Liu J., Meng H.R., Cao Y.M. 2009: CD4+CD25+Foxp3+ regulatory T cells prevent the development of Th1 immune response by inhibition of DC function during the early stage of Plasmodium yoelii infection in susceptible BALB/c mice. Folia Parasitol. 56: 242-250. Go to original source... Go to PubMed...