Malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. To successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. A significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. We have used fluorescence microscopy of Plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoite disappearance from the skin. Sporozoites injected into immunized mice were rapidly immobilized, did not appear to invade dermal blood vessels and became morphologically degraded within several hours. Strikingly, mosquitoes introduced significantly fewer sporozoites into immunized than into non-immunized mice, presumably by formation of an immune complex between soluble sporozoite antigens in the mosquito saliva and homologous host antibodies at the proboscis tip. These results indicate that protective antibodies directed against sporozoites may function both by reducing the numbers of sporozoites injected into immunized hosts and by inhibiting the movement of injected sporozoites into dermal blood vessels.
References
[1]
Sidjanski S, Vanderberg JP (1997) Delayed migration of Plasmodium sporozoites from the mosquito bite site to the blood. Am J Trop Med Hyg 57: 426–429.
[2]
Matsuoka H, Yoshida S, Hirai M, Ishii A (2002) A rodent malaria, Plasmodium berghei, is experimentally transmitted to mice by merely probing of infective mosquito, Anopheles stephensi. Parasitol Int 51: 17–23.
[3]
Vanderberg JP, Frevert U (2004) Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes. Int J Parasitol 34: 991–996.
[4]
Medica DL, Sinnis P (2005) Quantitative dynamics of Plasmodium yoelii sporozoite transmission by infected anopheline mosquitoes. Infect Immun 73: 4363–4369.
[5]
Amino R, Thiberge S, Martin B, Celli S, Shorte S, et al. (2006) Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 12: 220–224.
[6]
Yamauchi LM, Coppi A, Snounou G, Sinnis P (2007) Plasmodium sporozoites trickle out of the injection site. Cell Microbiol 9: 1215–1222.
[7]
Fairley NH (1947) Sidelights in malaria in man obtained by subinoculation experiments. Trans Roy Soc Trop Med Hyg 40: 621–676.
[8]
Jin Y, Kebaier C, Vanderberg J (2007) Direct microscopic quantification of dynamics of Plasmodium berghei sporozoite transmission from mosquitoes to mice. Infect Immun 75: 5532–5539.
[9]
Charoenvit Y, Mellouk S, Cole C, Bechara R, Leef MF, et al. (1991) Monoclonal, but not polyclonal, antibodies protect against Plasmodium yoelii sporozoites. J Immunol 146: 1020–1025.
[10]
Rickman LS, Jones TR, Long GW, Paparello S, Schneider I, et al. (1990) Plasmodium falciparum-infected Anopheles stephensi inconsistently transmit malaria to humans. Am J Trop Med Hyg 43: 441–445.
[11]
Stewart MJ, Vanderberg JP (1991) Malaria sporozoites release circumsporozoite protein from their apical end and translocate it along their surface. J Protozool 38: 411–421.
[12]
Golenda CF, Burge R, Schneider I (1992) Plasmodium falciparum and P. berghei: detection of sporozoites and the circumsporozoite proteins in the saliva of Anopheles stephensi mosquitoes. Parasitol Res 78: 563–569.
[13]
Beier JC, Vaughan JA, Madani A, Noden BH (1992) Plasmodium falciparum: release of circumsporozoite protein by sporozoites in the mosquito vector. Exp Parasitol 75: 248–256.
[14]
Williams RC Jr (1980) Immune Complexes in Clinical and Experimental Medicine. Cambridge, MA: Harvard University Press.
[15]
Padlan EA (1994) Antibody-Antigen Complexes. Boca Raton, FL: CRC Press.
[16]
Nussenzweig RS, Vanderberg JP, Sanabria Y, Most H (1972) Plasmodium berghei: accelerated clearance of sporozoites from blood as part of immune-mechanism in mice. Exp Parasitol 31: 88–97.
[17]
Sun P, Schwenk R, White K, Stoute JA, Cohen J, et al. (2003) Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-gamma. J Immunol 171: 6961–6967.
[18]
Hafalla JC, Cockburn IA, Zavala F (2006) Protective and pathogenic roles of CD8+ T cells during malaria infection. Parasite Immunol 28: 15–24.
[19]
Sterling CR, Aikawa M, Vanderberg JP (1973) The passage of Plasmodium berghei sporozoites through the salivary glands of Anopheles stephensi: an electron microscope study. J Parasitol 59: 593–605.
[20]
Vanderberg JP (1977) Plasmodium berghei: quantitation of sporozoites injected by mosquitoes feeding on a rodent host. Exp Parasitol 42: 169–181.
[21]
Frevert U, Engelmann S, Zougbede S, Stange J, Ng B, et al. (2005) Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol 3: e192. doi:10.1371/journal.pbio.0030192.
[22]
Vanderberg J, Gwadz R (1980) The transmission by mosquitoes of plasmodia in the laboratory. In: Kreier J, editor. Malaria: pathology, vector studies and culture. New York, N.Y.: Academic Press. pp. 154–218.
[23]
Amino R, Menard R, Frischknecht F (2005) In vivo imaging of malaria parasites–recent advances and future directions. Curr Opin Microbiol 8: 407–414.
[24]
Tarun AS, Baer K, Dumpit RF, Gray S, Lejarcegui N, et al. (2006) Quantitative isolation and in vivo imaging of malaria parasite liver stages. Int J Parasitol 36: 1283–1293.
[25]
Evans NT, Naylor PF, Rowlinson G (1981) Diffusion of oxygen through the mouse ear. Br J Dermatol 105: 45–56.
[26]
Mack SR, Vanderberg JP, Nawrot R (1978) Column separation of Plasmodium berghei sporozoites. J Parasitol 64: 166–168.
[27]
Frischknecht F, Baldacci P, Martin B, Zimmer C, Thiberge S, et al. (2004) Imaging movement of malaria parasites during transmission by Anopheles mosquitoes. Cell Microbiol 6: 687–694.
[28]
Chai SK, Clavijo P, Tam JP, Zavala F (1992) Immunogenic properties of multiple antigen peptide systems containing defined T and B epitopes. Journal of Immunology 149: 2385–2390.
