Ageing of Plasmodium falciparum malaria sporozoites alters their motility, infectivity and reduces immune activation in vitro.
Plasmodium falciparum
Immunogenicity
Malaria
Motility
Sporozoites
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
19 Apr 2024
19 Apr 2024
Historique:
received:
23
01
2024
accepted:
12
04
2024
medline:
20
4
2024
pubmed:
20
4
2024
entrez:
19
4
2024
Statut:
epublish
Résumé
Sporozoites (SPZ), the infective form of Plasmodium falciparum malaria, can be inoculated into the human host skin by Anopheline mosquitoes. These SPZ migrate at approximately 1 µm/s to find a blood vessel and travel to the liver where they infect hepatocytes and multiply. In the skin they are still low in number (50-100 SPZ) and vulnerable to immune attack by antibodies and skin macrophages. This is why whole SPZ and SPZ proteins are used as the basis for most malaria vaccines currently deployed and undergoing late clinical testing. Mosquitoes typically inoculate SPZ into a human host between 14 and 25 days after their previous infective blood meal. However, it is unknown whether residing time within the mosquito affects SPZ condition, infectivity or immunogenicity. This study aimed to unravel how the age of P. falciparum SPZ in salivary glands (14, 17, or 20 days post blood meal) affects their infectivity and the ensuing immune responses. SPZ numbers, viability by live/dead staining, motility using dedicated sporozoite motility orienting and organizing tool software (SMOOT), and infectivity of HC-04.j7 liver cells at 14, 17 and 20 days after mosquito feeding have been investigated. In vitro co-culture assays with SPZ stimulated monocyte-derived macrophages (MoMɸ) and CD8 SPZ age did not result in different SPZ numbers or viability. However, a markedly different motility pattern, whereby motility decreased from 89% at day 14 to 80% at day 17 and 71% at day 20 was observed (p ≤ 0.0001). Similarly, infectivity of day 20 SPZ dropped to ~ 50% compared with day 14 SPZ (p = 0.004). MoMɸ were better able to take up day 14 SPZ than day 20 SPZ (from 7.6% to 4.1%, p = 0.03) and displayed an increased expression of pro-inflammatory CD80, IL-6 (p = 0.005), regulatory markers PDL1 (p = 0.02), IL-10 (p = 0.009) and cytokines upon phagocytosis of younger SPZ. Interestingly, co-culture of these cells with CD8 Overall, this data is a first step in enhancing the understanding of how mosquito residing time affects P. falciparum SPZ and could impact the understanding of the P. falciparum infectious reservoir and the potency of whole SPZ vaccines.
Sections du résumé
BACKGROUND
BACKGROUND
Sporozoites (SPZ), the infective form of Plasmodium falciparum malaria, can be inoculated into the human host skin by Anopheline mosquitoes. These SPZ migrate at approximately 1 µm/s to find a blood vessel and travel to the liver where they infect hepatocytes and multiply. In the skin they are still low in number (50-100 SPZ) and vulnerable to immune attack by antibodies and skin macrophages. This is why whole SPZ and SPZ proteins are used as the basis for most malaria vaccines currently deployed and undergoing late clinical testing. Mosquitoes typically inoculate SPZ into a human host between 14 and 25 days after their previous infective blood meal. However, it is unknown whether residing time within the mosquito affects SPZ condition, infectivity or immunogenicity. This study aimed to unravel how the age of P. falciparum SPZ in salivary glands (14, 17, or 20 days post blood meal) affects their infectivity and the ensuing immune responses.
METHODS
METHODS
SPZ numbers, viability by live/dead staining, motility using dedicated sporozoite motility orienting and organizing tool software (SMOOT), and infectivity of HC-04.j7 liver cells at 14, 17 and 20 days after mosquito feeding have been investigated. In vitro co-culture assays with SPZ stimulated monocyte-derived macrophages (MoMɸ) and CD8
RESULTS
RESULTS
SPZ age did not result in different SPZ numbers or viability. However, a markedly different motility pattern, whereby motility decreased from 89% at day 14 to 80% at day 17 and 71% at day 20 was observed (p ≤ 0.0001). Similarly, infectivity of day 20 SPZ dropped to ~ 50% compared with day 14 SPZ (p = 0.004). MoMɸ were better able to take up day 14 SPZ than day 20 SPZ (from 7.6% to 4.1%, p = 0.03) and displayed an increased expression of pro-inflammatory CD80, IL-6 (p = 0.005), regulatory markers PDL1 (p = 0.02), IL-10 (p = 0.009) and cytokines upon phagocytosis of younger SPZ. Interestingly, co-culture of these cells with CD8
CONCLUSION
CONCLUSIONS
Overall, this data is a first step in enhancing the understanding of how mosquito residing time affects P. falciparum SPZ and could impact the understanding of the P. falciparum infectious reservoir and the potency of whole SPZ vaccines.
Identifiants
pubmed: 38641838
doi: 10.1186/s12936-024-04946-7
pii: 10.1186/s12936-024-04946-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111Subventions
Organisme : VIDI fellowship, Dutch Scientific Organisation
ID : 09150172010035
Informations de copyright
© 2024. The Author(s).
Références
WHO. World Malaria Report 2022. Geneva: World Health Organization; 2022
Snow RW. Global malaria eradication and the importance of Plasmodium falciparum epidemiology in Africa. BMC Med. 2015;13:23.
pubmed: 25644195
pmcid: 4314741
doi: 10.1186/s12916-014-0254-7
Mishra S, Nussenzweig RS, Nussenzweig V. Antibodies to Plasmodium circumsporozoite protein (CSP) inhibit sporozoite’s cell traversal activity. J Immunol Methods. 2012;377:47–52.
pubmed: 22306356
pmcid: 3310221
doi: 10.1016/j.jim.2012.01.009
Walther M. Advances in vaccine development against the pre-erythrocytic stage of Plasmodium falciparum malaria. Expert Rev Vaccines. 2006;5:81–93.
pubmed: 16451110
doi: 10.1586/14760584.5.1.81
Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, et al. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insight. 2017;2: e89154.
pubmed: 28097230
pmcid: 5214067
doi: 10.1172/jci.insight.89154
Molina-Franky J, Cuy-Chaparro L, Camargo A, Reyes C, Gomez M, Salamanca DR, et al. Plasmodium falciparum pre-erythrocytic stage vaccine development. Malar J. 2020;19:56.
pubmed: 32013956
pmcid: 6998842
doi: 10.1186/s12936-020-3141-z
Ghosh AK, Jacobs-Lorena M. Plasmodium sporozoite invasion of the mosquito salivary gland. Curr Opin Microbiol. 2009;12:394–400.
pubmed: 19608457
pmcid: 2759692
doi: 10.1016/j.mib.2009.06.010
Bennink S, Kiesow MJ, Pradel G. The development of malaria parasites in the mosquito midgut. Cell Microbiol. 2016;18:905–18.
pubmed: 27111866
pmcid: 5089571
doi: 10.1111/cmi.12604
Schleicher TR, Yang J, Freudzon M, Rembisz A, Craft S, Hamilton M, et al. A mosquito salivary gland protein partially inhibits Plasmodium sporozoite cell traversal and transmission. Nat Commun. 2018;9:2908.
pubmed: 30046053
pmcid: 6060088
doi: 10.1038/s41467-018-05374-3
Lindner SE, Swearingen KE, Shears MJ, Sebastian A, Walker MP, Vrana EN, et al. Addendum: Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites. Nat Commun. 2022;13:283.
pubmed: 34992211
pmcid: 8738726
doi: 10.1038/s41467-021-27767-7
Porter RJ, Laird RL, Dusseau EM. Studies on malarial sporozoites. II. Effect of age and dosage of sporozoites on their infectiousness. Exp Parasitol. 1954;3:276–374.
doi: 10.1016/0014-4894(54)90026-0
Gillies MT, Wilkes TJ. A study of the age-composition of populations of Anopheles gambiae Giles and A. funestus Giles in North-Eastern Tanzania. Bull Entomol Res. 1965;56:237–62.
pubmed: 5854754
doi: 10.1017/S0007485300056339
Lines JD, Wilkes TJ, Lyimo EO. Human malaria infectiousness measured by age-specific sporozoite rates in Anopheles gambiae in Tanzania. Parasitology. 1991;102:167–77.
pubmed: 1852484
doi: 10.1017/S0031182000062454
Cockburn IA, Seder RA. Malaria prevention: from immunological concepts to effective vaccines and protective antibodies. Nat Immunol. 2018;19:1199–211.
pubmed: 30333613
doi: 10.1038/s41590-018-0228-6
Zhu F, Zheng H, Chen S, Zhang K, Qin X, Zhang J, et al. Malaria oocysts require circumsporozoite protein to evade mosquito immunity. Nat Commun. 2022;13:3208.
pubmed: 35680915
pmcid: 9184642
doi: 10.1038/s41467-022-30988-z
Sultan AA, Thathy V, Frevert U, Robson KJ, Crisanti A, Nussenzweig V, et al. TRAP is necessary for gliding motility and infectivity of Plasmodium sporozoites. Cell. 1997;90:511–22.
pubmed: 9267031
doi: 10.1016/S0092-8674(00)80511-5
Corradin G, Levitskaya J. Priming of CD8(+) T cell responses to liver stage malaria parasite antigens. Front Immunol. 2014;5:527.
pubmed: 25414698
pmcid: 4220712
doi: 10.3389/fimmu.2014.00527
Osii RS, Otto TD, Garside P, Ndungu FM, Brewer JM. The impact of malaria parasites on dendritic cell-T cell interaction. Front Immunol. 2020;11:1597.
pubmed: 32793231
pmcid: 7393936
doi: 10.3389/fimmu.2020.01597
Winkel BMF, Pelgrom LR, van Schuijlenburg R, Baalbergen E, Ganesh MS, Gerritsma H, et al. Plasmodium sporozoites induce regulatory macrophages. PLoS Pathog. 2020;16: e1008799.
pubmed: 32898164
pmcid: 7500643
doi: 10.1371/journal.ppat.1008799
Chakravarty S, Cockburn IA, Kuk S, Overstreet MG, Sacci JB, Zavala F. CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nat Med. 2007;13:1035–41.
pubmed: 17704784
doi: 10.1038/nm1628
Ejigiri I, Sinnis P. Plasmodium sporozoite-host interactions from the dermis to the hepatocyte. Curr Opin Microbiol. 2009;12:401–7.
pubmed: 19608456
pmcid: 2725221
doi: 10.1016/j.mib.2009.06.006
Oneko M, Steinhardt LC, Yego R, Wiegand RE, Swanson PA, Kc N, et al. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. Nat Med. 2021;27:1636–45.
pubmed: 34518679
doi: 10.1038/s41591-021-01470-y
Ponnudurai T, Leeuwenberg AD, Meuwissen JH. Chloroquine sensitivity of isolates of Plasmodium falciparum adapted to in vitro culture. Trop Geogr Med. 1981;33:50–4.
pubmed: 7018038
Lensen A, Bril A, van de Vegte M, van Gemert GJ, Eling W, Sauerwein R. Plasmodium falciparum: infectivity of cultured, synchronized gametocytes to mosquitoes. Exp Parasitol. 1999;91:101–3.
pubmed: 9920049
doi: 10.1006/expr.1998.4354
Ponnudurai T, Lensen AH, Van Gemert GJ, Bensink MP, Bolmer M, Meuwissen JH. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology. 1989;98:165–73.
pubmed: 2668861
doi: 10.1017/S0031182000062065
Churcher TS, Blagborough AM, Delves M, Ramakrishnan C, Kapulu MC, Williams AR, et al. Measuring the blockade of malaria transmission–an analysis of the standard membrane feeding assay. Int J Parasitol. 2012;42:1037–44.
pubmed: 23023048
doi: 10.1016/j.ijpara.2012.09.002
Coleman J, Juhn J, James AA. Dissection of midgut and salivary glands from Ae. aegypti mosquitoes. J Vis Exp. 2007;5:228.
Nardin EH, Nussenzweig V, Nussenzweig RS, Collins WE, Harinasuta KT, Tapchaisri P, et al. Circumsporozoite proteins of human malaria parasites Plasmodium falciparum and Plasmodium vivax. J Exp Med. 1982;156:20–30.
pubmed: 7045272
doi: 10.1084/jem.156.1.20
Winkel BMF, de Korne CM, van Oosterom MN, Staphorst D, Meijhuis M, Baalbergen E, et al. Quantification of wild-type and radiation attenuated Plasmodium falciparum sporozoite motility in human skin. Sci Rep. 2019;9:13436.
pubmed: 31530862
pmcid: 6748968
doi: 10.1038/s41598-019-49895-3
de Korne CM, van Schuijlenburg R, Sijtsma JC, de Bes HM, Baalbergen E, Azargoshasb S, et al. Sporozoite motility as a quantitative readout for anti-CSP antibody inhibition. Sci Rep. 2022;12:17194.
pubmed: 36229488
pmcid: 9561690
doi: 10.1038/s41598-022-22154-8
de Korne CM, Lageschaar LT, van Oosterom MN, Baalbergen E, Winkel BMF, Chevalley-Maurel SC, et al. Regulation of Plasmodium sporozoite motility by formulation components. Malar J. 2019;18:155.
pubmed: 31046772
pmcid: 6498664
doi: 10.1186/s12936-019-2794-y
Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am J Respir Cell Mol Biol. 2015;53:676–88.
pubmed: 25870903
doi: 10.1165/rcmb.2015-0012OC
Hussaarts L, Smits HH, Schramm G, van der Ham AJ, van der Zon GC, Haas H, et al. Rapamycin and omega-1: mTOR-dependent and -independent Th2 skewing by human dendritic cells. Immunol Cell Biol. 2013;91:486–9.
pubmed: 23835553
doi: 10.1038/icb.2013.31
Dranka BP, Benavides GA, Diers AR, Giordano S, Zelickson BR, Reily C, et al. Assessing bioenergetic function in response to oxidative stress by metabolic profiling. Free Radic Biol Med. 2011;51:1621–35.
pubmed: 21872656
pmcid: 3548422
doi: 10.1016/j.freeradbiomed.2011.08.005
Mota MM, Pradel G, Vanderberg JP, Hafalla JC, Frevert U, Nussenzweig RS, et al. Migration of Plasmodium sporozoites through cells before infection. Science. 2001;291:141–4.
pubmed: 11141568
doi: 10.1126/science.291.5501.141
Wang Q, Fujioka H, Nussenzweig V. Exit of Plasmodium sporozoites from oocysts is an active process that involves the circumsporozoite protein. PLoS Pathog. 2005;1: e9.
pubmed: 16201021
pmcid: 1238744
doi: 10.1371/journal.ppat.0010009
Real E, Howick VM, Dahalan FA, Witmer K, Cudini J, Andradi-Brown C, et al. A single-cell atlas of Plasmodium falciparum transmission through the mosquito. Nat Commun. 2021;12:3196.
pubmed: 34045457
pmcid: 8159942
doi: 10.1038/s41467-021-23434-z
Luckhart S, Riehle MA. Midgut mitochondrial function as a gatekeeper for malaria parasite infection and development in the mosquito host. Front Cell Infect Microbiol. 2020;10: 593159.
pubmed: 33363053
pmcid: 7759495
doi: 10.3389/fcimb.2020.593159
Foquet L, Hermsen CC, van Gemert GJ, Van Braeckel E, Weening KE, Sauerwein R, et al. Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection. J Clin Invest. 2014;124:140–4.
pubmed: 24292709
doi: 10.1172/JCI70349
Swearingen KE, Lindner SE, Shi L, Shears MJ, Harupa A, Hopp CS, et al. Interrogating the Plasmodium sporozoite surface: identification of surface-exposed proteins and demonstration of glycosylation on CSP and TRAP by mass spectrometry-based proteomics. PLoS Pathog. 2016;12: e1005606.
pubmed: 27128092
pmcid: 4851412
doi: 10.1371/journal.ppat.1005606
Beyer K, Kracht S, Kehrer J, Singer M, Klug D, Frischknecht F. Limited Plasmodium sporozoite gliding motility in the absence of TRAP family adhesins. Malar J. 2021;20:430.
pubmed: 34717635
pmcid: 8557484
doi: 10.1186/s12936-021-03960-3
Arama C, Troye-Blomberg M. The path of malaria vaccine development: challenges and perspectives. J Intern Med. 2014;275:456–66.
pubmed: 24635625
doi: 10.1111/joim.12223
Butler NS, Vaughan AM, Harty JT, Kappe SH. Whole parasite vaccination approaches for prevention of malaria infection. Trends Immunol. 2012;33:247–54.
pubmed: 22405559
doi: 10.1016/j.it.2012.02.001
Itsara LS, Zhou Y, Do J, Grieser AM, Vaughan AM, Ghosh AK. The development of whole sporozoite vaccines for Plasmodium falciparum malaria. Front Immunol. 2018;9:2748.
pubmed: 30619241
pmcid: 6297750
doi: 10.3389/fimmu.2018.02748
Sirima SB, Ouedraogo A, Tiono AB, Kabore JM, Bougouma EC, Ouattara MS, et al. A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria. Sci Transl Med. 2022;14:eabj3776.
pubmed: 36475905
pmcid: 10041996
doi: 10.1126/scitranslmed.abj3776