The Skin: Where Malaria Infection and the Host Immune Response Begin

Overview

Journal Semin Immunopathol

Publisher Springer

Specialties Allergy & Immunology
Pathology

Date 2012 Oct 12

PMID 23053392

Citations 47

Authors

Photini Sinnis

Fidel Zavala

Affiliations

Soon will be listed here.

Abstract

Infection by malaria parasites begins with the inoculation of sporozoites into the skin of the host. The early events following sporozoite deposition in the dermis are critical for both the establishment of malaria infection and for the induction of protective immune responses. The initial sporozoite inoculum is generally low, and only a small percentage of these sporozoites successfully reach the liver and grow to the next life cycle stage, making this a significant bottleneck for the parasite. Recent studies highlight the importance of sporozoite motility and host cell traversal in dermal exit. Importantly, protective immune responses against sporozoites and liver stages of Plasmodium are induced by dendritic cells in the lymph node draining the skin inoculation site. The cellular, molecular, and immunological events that occur in the skin and associated lymph nodes are the topic of this review.

Citing Articles

Early Activation of Lung CD8 T Cells After Immunization with Live Malaria Sporozoites.

van Schuijlenburg R, Naar C, van der Wees S, Chevalley-Maurel S, Duszenko N, de Bes-Roeleveld H Pathog Immun. 2025; 10(2):46-68.

PMID: 40062354 PMC: 11888604. DOI: 10.20411/pai.v10i2.794.

Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.

Segovia X, Srivastava B, Serrato-Arroyo S, Guerrero A, Huijben S Malar J. 2025; 24(1):65.

PMID: 40025552 PMC: 11871665. DOI: 10.1186/s12936-025-05286-w.

A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and as a Combination Vaccine Candidate.

Xia M, Huang P, Vago F, Jiang W, Jiang X, Tan M Vaccines (Basel). 2025; 13(1.

PMID: 39852813 PMC: 11769195. DOI: 10.3390/vaccines13010034.

sporozoite shows distinct motility patterns in responses to three-dimensional environments.

Liu Z, Li S, Anantha P, Thanakornsombut T, Wu L, Chen J iScience. 2024; 27(8):110463.

PMID: 39129829 PMC: 11315120. DOI: 10.1016/j.isci.2024.110463.

Cytokine gene polymorphisms implicated in the pathogenesis of infection outcome.

Segbefia S, Asandem D, Amoah L, Kusi K Front Immunol. 2024; 15:1285411.

PMID: 38404582 PMC: 10884311. DOI: 10.3389/fimmu.2024.1285411.

References

Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G . Development of the malaria parasite in the skin of the mammalian host. Proc Natl Acad Sci U S A. 2010; 107(43):18640-5. PMC: 2972976. DOI: 10.1073/pnas.1009346107. View

Voza T, Miller J, Kappe S, Sinnis P . Extrahepatic exoerythrocytic forms of rodent malaria parasites at the site of inoculation: clearance after immunization, susceptibility to primaquine, and contribution to blood-stage infection. Infect Immun. 2012; 80(6):2158-64. PMC: 3370592. DOI: 10.1128/IAI.00246-12. View

Rosenberg R, Wirtz R, Schneider I, Burge R . An estimation of the number of malaria sporozoites ejected by a feeding mosquito. Trans R Soc Trop Med Hyg. 1990; 84(2):209-12. DOI: 10.1016/0035-9203(90)90258-g. View

Vanderberg J, Nussenzweig R, MOST H, Orton C . Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. II. Effects of radiation on sporozoites. J Parasitol. 1968; 54(6):1175-80. View

Sidjanski S, Vanderberg J . Delayed migration of Plasmodium sporozoites from the mosquito bite site to the blood. Am J Trop Med Hyg. 1997; 57(4):426-9. DOI: 10.4269/ajtmh.1997.57.426. View

Hafalla J, Rai U, Morrot A, Bernal-Rubio D, Zavala F, Rodriguez A . Priming of CD8+ T cell responses following immunization with heat-killed Plasmodium sporozoites. Eur J Immunol. 2006; 36(5):1179-86. DOI: 10.1002/eji.200535712. View

Leitner W, Bergmann-Leitner E, Angov E . Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. Malar J. 2010; 9:145. PMC: 2904356. DOI: 10.1186/1475-2875-9-145. View

Klenerman P, Hill A . T cells and viral persistence: lessons from diverse infections. Nat Immunol. 2005; 6(9):873-9. DOI: 10.1038/ni1241. View

Ejigiri I, Ragheb D, Pino P, Coppi A, Bennett B, Soldati-Favre D . Shedding of TRAP by a rhomboid protease from the malaria sporozoite surface is essential for gliding motility and sporozoite infectivity. PLoS Pathog. 2012; 8(7):e1002725. PMC: 3406075. DOI: 10.1371/journal.ppat.1002725. View

10.

Silvie O, Semblat J, Franetich J, Hannoun L, Eling W, Mazier D . Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines. Parasite Immunol. 2002; 24(4):221-3. DOI: 10.1046/j.1365-3024.2002.00450.x. View

11.

Amino R, Giovannini D, Thiberge S, Gueirard P, Boisson B, Dubremetz J . Host cell traversal is important for progression of the malaria parasite through the dermis to the liver. Cell Host Microbe. 2008; 3(2):88-96. DOI: 10.1016/j.chom.2007.12.007. View

12.

Sultan A, Thathy V, Frevert U, Robson K, Crisanti A, NUSSENZWEIG V . TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites. Cell. 1997; 90(3):511-22. DOI: 10.1016/s0092-8674(00)80511-5. View

13.

Jung S, Unutmaz D, Wong P, Sano G, de Los Santos K, Sparwasser T . In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity. 2002; 17(2):211-20. PMC: 3689299. DOI: 10.1016/s1074-7613(02)00365-5. View

14.

Ishino T, Yano K, Chinzei Y, Yuda M . Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer. PLoS Biol. 2004; 2(1):E4. PMC: 314464. DOI: 10.1371/journal.pbio.0020004. View

15.

Amino R, Thiberge S, Martin B, Celli S, Shorte S, Frischknecht F . Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med. 2006; 12(2):220-4. DOI: 10.1038/nm1350. View

16.

Medica D, Sinnis P . Quantitative dynamics of Plasmodium yoelii sporozoite transmission by infected anopheline mosquitoes. Infect Immun. 2005; 73(7):4363-9. PMC: 1168603. DOI: 10.1128/IAI.73.7.4363-4369.2005. View

17.

Bursch L, Wang L, Igyarto B, Kissenpfennig A, Malissen B, Kaplan D . Identification of a novel population of Langerin+ dendritic cells. J Exp Med. 2007; 204(13):3147-56. PMC: 2150989. DOI: 10.1084/jem.20071966. View

18.

Wilson N, Behrens G, Lundie R, Smith C, Waithman J, Young L . Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. Nat Immunol. 2006; 7(2):165-72. DOI: 10.1038/ni1300. View

19.

Allan R, Waithman J, Bedoui S, Jones C, Villadangos J, Zhan Y . Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006; 25(1):153-62. DOI: 10.1016/j.immuni.2006.04.017. View

20.

Ishino T, Chinzei Y, Yuda M . A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection. Cell Microbiol. 2005; 7(2):199-208. DOI: 10.1111/j.1462-5822.2004.00447.x. View