Resistance and Susceptibility to Malarial Infection: A Host Defense Strategy against Malaria
Abstract
Background: In an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence.
Methods: Two groups of mice from different genotypes were used (C57BL/6 (B6) and DBA/2 mice). The mice were infected with a virulent parasite line Plasmodium yoelii17XL (P. yoelii17XL). Parasitemia, hematocrit value and lymphocytes yielded by livers and spleens were evaluated. Fluorescence Activated Cell Sorting (FACS) analysis illustrated phenotypic characterization of lymphocytes.
Results: Infection with P. yoelii17XL did not result in thedeath of DBA/2 mice. In contrast,B6 mice developed significantly high parasitemia and succumbed to death. Using (FACS) analysis, DBA/2 mice were found to experience a marked expansion of interleukin (IL)-2Rb+ CD3int cells and gd T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 mice.
Conclusion: The outcome of murine malaria infections depends on the dynamic interplay between the immune-mediator and the genotype of the host.
Burt RA, Marshall VM, Wagglen J, Rodda FR, Senyschen D, Baldwin TM, Buckingham LA, Foote SJ. Mice that are congenic for the char2 locus are susceptible to malaria. Infect Immun. 2002; 70: 4750–4753.
Fortin A, Stevenson MM, Gros P. Complex genetic control of susceptibility to malaria in mice. Genes Immun. 2002; 3: 177– 186.
Knowles G, Walliker D. Variable expression of virulence in the rodent malaria Plasmodium yoelii. Parasitology. 1980; 81: 211.
Stevenson MM, Lyanga JJ, Skamene E. Murine malaria: Genetic control of resistance to Plasmo-dium chabaudi. Infect Immun. 1982; 38230.
Stevenson MM, Skamene E. Murine malaria: resistance of AXB/BXA recombinant inbred mice to Plasmodium chabaudi. Infect Immun. 1985; 47: 452.
Sayles PC, Wassom DL. Immunoregulation in murine malaria. Susceptibility of inbred mice to infection with Plasmodium yoelii depends on the dynamic interplay of host and parasite genes. J Immunol. 1988; 141: 241–8.
Haque A, Echchannaoui H, Seguin R, Schwartzman J, Kasper LH, Haque S. Cerebral malaria in mice. Interleukin-2 treatment in-duces accumulation of T cells in the brain and alters resistant mice to susceptible-like phe-notype. Am J Pathol. 2001; 158:163–72.
Ashman RB, Papadimitriou JM, Fulurija A, Drysdale KE, Farah CS, Naidoo O, Got-jamanos T. Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice. Microb Pathog. 2003; 34: 103–13.
Mannoor MK, Weerasinghe A, Halder RC, Morshed SRM, Ariyasinghe A, Watanabe H, Sekikawa H, Abo T. Resistance to malarial in-
fection is achieved by the cooperation of NK1.1+ and NK1.1– subsets of intermediate TCR cells which are constituents of innate im-munity. Cell Immunol. 2001; 211:96–104.
Weerasinghe A, Sekikawa H, Watanabe H, Mannoor K, Morshed SR, Halder RC, Kawa-mura T, Kosaka T, Miyaji C, Kawamura H, Seki S, Abo T. Association of intermediate T cell receptor cells, mainly their NK1.1– subset with protection from malaria. Cell Immunol. 2001; 207:28–35.
Mannoor MK, Halder RC, Morshed SRM, Ariyasinghe A, Bakir HY, Kawamura H, Watanabe H, Sekikawa H, Abo T. Essential role of extrathymic T cells in protection against malaria. J Immunol. 2002; 169:301–6.
Halder RC, Abe T, Mannoor MK, Morshed SR, Ariyasinghe A, Watanabe H, Kawamura H, Sekikawa H, Hamada H, Nishiyama Y, Ishika-wa H, Toba K, Abo T. Onset of hepatic eryth-ropoiesis after malarial infection in mice. Para-sitol Int 2003; 52:259–68.
Watanabe H, Miyaji C, Kawachi Y, Iiai T, Ohtsuka K, Iwanaga T, Takahashi-Iwanaga H, Abo T. Relationships between intermediate TCR cells and NK1.1+ T cells in various im-mune organs. NK1.1+ T cells are present with-in a population of intermediate TCR cells. J Immunol. 1995; 155:2972–83.
Watanabe H, Miyaji C, Seki S, Abo T. c-kit+ stem cells and thymocyte precursors in the liv-ers of adult mice. J Exp Med. 1996; 184: 687–93.
Bakir HY, Tomiyama C, Abo T. Cytokine pro-file of murine malaria: stage related production of inflammatory and anti-inflammatory cyto-kines. Biomed Res. 2011; 32(3): 203-8
Miyaji C, Watanabe H, Miyakawa R, Yoko-yama H, Tsukada C, Ishimoto Y, Abo T. Iden-tification of effector cells for TNF-mediated cytotoxicity against WEHI164S cells. Cell Im-munol. 2002; 216:43–9.
Miyakawa R, Miyaji C, Watanabe H, Yoko-yama H, Tsukada C, Asakura H, Abo T. Un-conventional NK1.1– intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus- host disease. Eur J Immunol. 2002; 32: 2521–31.
Raberg L, Sim D, Read AF. Disentangling ge-netic variation for resistance and tolerance to infectious diseases in animals. Science. 2007; 318: 812– 814.
Schneider DS, Ayres JS. Two ways to survive infection: What resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol. 2008; 8: 889 – 895.
Chen G, Feng H, Liu J, Qi ZM, Wu Y, Guo SY, Li DM, Wang JC, Cao YM. Characteriza-tion of immune responses to single or mixed infections with P. yoelii 17XL and P. chabaudi AS in different strains of mice. Parasitol Int. 2010; 59(3): 400-6.
Wang GG, Chen G, Feng H, Liu J, Jiang YJ, Shang H, Cao YM. Plasmodium chabaudi AS: dis-tinct CD4 (+) CD25 (+) Foxp3 (+) regulatory T cell responses during infection in DBA/2 and BALB/c mice. Parasitol Int. 2013; 62(1): 24-31
Epiphanio S, Campos MG, Pamplona A et al. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice. PLoS Pathog. 2010; 20 (5): 1-10
Ortolan LS, Sercundes MK, Barboza R et al. Predictive Criteria to Study the Pathogenesis of Malaria-Associated ALI/ARDS in Mice. Medi-ator Inflamm. 2014; 872464: 1-12.
Azcarate IG, Marin-Garcia P, Kamali AN, Perez-Benavente S, Puyet A, Diez A, Bautista JM. Differential immune response associated to malaria outcome is detectable in peripheral blood following Plasmodium yoelii infection in mice. PLoS One. 2014; 23: 9(1): 85664.
Cheng Q, Zhang Q, Xu X, Yin L, Sun L, Lin X, Dong C, Pan W. MAPK phosphotase 5 de-ficiency contributes to protection against blood stage Plasmodium yoelii 17 XL infection in mice. J Immunol. 2014; 15: 192(8): 3686- 96.
Bakir HY, Tomiyama-Miyaji C, Watanabe H, Nagura T, Kawamura T, Sekikawa H and Abo T. Reasons why DBA/2 mice are resistant to malarial infection: Expansion of CD3intB220+ gamma/delta T cells with double-negative CD4-8- phenotype in the liver. Immunology. 2006; 117: 127-135.
Oya, H, Kawamura T, Shimizu T, Bannai M, Kawamura H, Min- agawa, M, Watanabe H, Hatakeyama K, Abo T. The differential effect of stress on natural killer T (NKT) and NK cell function. Clin Exp Immunol. 2000; 121: 384–390.
Wickramasinghe, SN, Looareesuwan, S, Na-gachinta B, White NJ. Dyserythropoiesis and ineffective erythropoiesis in Plasmodium vivax malaria. Br J Haematol. 1989; 72: 91–99.
Salmon MG, De Souza JB, Butcher GA, Play-fair JH. Pre- mature removal of uninfected erythrocytes during malarial infection of nor-mal and immune-deficient mice. Clin Exp Im-munol. 1997;108: 471–476.
McDevitt, MA, Xie J, Gordeuk V, Bucala R. The anemia of malaria infection: role of inflam-matory cytokines. Current Hematol Reports. 2004; 3: 97–106.
Seixas E and Ostler D. Plasmodium chabaudi chabaudi (AS): Differential cellular responses to infection in resistant and susceptible mice. Exp Parasitol. 2005; 110: 394– 405
Bakir HY, Sayed FG, Abdel-Rahman SM, Hamza AI, Mahmoud AE, Galal LA, Attia RA. Comparative study between non lethal and le-thal strains of Plasmodium yoelii with reference to its immunological aspect. J Egypt Soc Parasitol. 2009; 39: 1-10.
Bakir HY, Elmatary AM. Protective function of intermediate T cells against malaria infection in mice with different genetic background. IJBR. 2014; 05 (7)
Good MF, Engwerda C. Defying malaria: Arming T cell to halt malaria. Nat Med. 2011; 17: 49- 51
Janeway CA. Frontiers of the immune system. Nature. 1988; 373: 255–257.
Ferrick DA, Schrenzel MD, Mulvania T, Itseih B, Ferlin WG, Lepper H. Differential produc-tion of interferon-gamma and interleukin-4 in response to Th1 and Th2 stimulating patho-gens by gamma delta T cells in vivo. Nature. 1995; 373: 255–257.
Ho M, Webster HK, Tonqtacoe P, Pattana-panyasat K, Weidanz WP. Increased gamma delta T cells in acute Plasmodium falciparum ma-laria. Immunol Lett. 1990; 25: 139–142.
Roussilhon C, Agrapart M, Ballet JJ. T lym-phocytes bearing gamma delta T cell receptor in patients with acute Plasmodium falciparum ma-laria. J Infect Dis. 1990; 162: 283–285.
Elloso MM, Van der Heyde HC, Vande Waa DD. Manning DD, Weidanz WP. Inhibition of Plasmodium falciparum in vitro by human gamma delta T cells. J Immunol. 1994; 153: 1187–1194.
Van der Heyde HC, Elloso MM, Chang WL, Kaplan M, Manning DD, Weidanz WP. Gamma delta T cell function in cell-mediated immunity to acute blood stage Plasmodium chabaudi adami malaria. J Immunol. 1995; 154:3985–3990.
Weidanz Wp, LaFleur G, Brown A, Burns JM Jr, Gramaglia I, Van der Heyde HC. Gamma delta T cells but not NK cells are essential for cell-mediated immunity against Plasmodium chabaudi malaria. Infect Immun. 2010; 78(10): 4331- 40
Langhorne J, Goodier M, Behr C, Dubois P. Is there a role for gamma delta T cells in malaria? Immunol Today. 1992; 13:298–300.
Davidson WF, Dumont FJ, Bedigian HG, Fowlkes BJ, Morse HC. Phenotypic, functional, and molecular genetic comparisons of the ab-normal lymphoid cells of C3H-lpr/lpr and
C3H-gld/gld mice. J Immunol. 1986; 136 :4075–84.
Shivakumar S, Tsokos GC, Datta SK. T cell receptor alpha beta expressing double-negative (CD4–/CD8–) and CD4+T helper cells in hu-mans augment the production of pathogenic anti-DNA auto-antibodies associated with lu-pus nephritis. J Immunol. 1989; 143:103–12.
Yamagiwa S, Kuwano Y, Hasegawa K, Sato K, Ohtsuka K, Iiai T, Tomiyama K, Watanabe H, Sugahara S, Seki S, Asakura H, Abo T. Exist-ence of a small population of IL-2Rbhi TCRint cells in SCG and MRL-lpr/lpr mice which pro-duce normal Fas mRNA and Fas molecules from the lpr gene. Eur J Immunol. 1996; 26:1409–16.
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Issue | Vol 10 No 4 (2015) | |
Section | Original Article(s) | |
Keywords | ||
Malaria Immune cells DBA/2 mice |
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