Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite.

Grand, Morgane; Waqasi, Mishelle; Demarta-Gatsi, Claudia; Wei, Yu; Peronet, Roger; Commere, Pierre-Henri; Puig, Amandine; Axelrod, Jonathan; Caldelari, Reto; Heussler, Volker; Amino, Rogerio; Mecheri, Salaheddine (2020). Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite. Frontiers in immunology, 11, p. 585502. Frontiers Research Foundation 10.3389/fimmu.2020.585502

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Deciphering the mechanisms by which Plasmodium parasites develop inside hepatocytes is an important step toward the understanding of malaria pathogenesis. We propose that the nature and the magnitude of the inflammatory response in the liver are key for the establishment of the infection. Here, we used mice deficient in the multidrug resistance-2 gene (Mdr2-/-)-encoded phospholipid flippase leading to the development of liver inflammation. Infection of Mdr2-/- mice with Plasmodium berghei ANKA (PbANKA) sporozoites (SPZ) resulted in the blockade of hepatic exo-erythrocytic forms (EEFs) with no further development into blood stage parasites. Interestingly, cultured primary hepatocytes from mutant and wild-type mice are equally effective in supporting EEF development. The abortive infection resulted in a long-lasting immunity in Mdr2-/- mice against infectious SPZ where neutrophils and IL-6 appear as key effector components along with CD8+ and CD4+ effector and central memory T cells. Inflammation-induced breakdown of liver tolerance promotes anti-parasite immunity and provides new approaches for the design of effective vaccines against malaria disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology
08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria

UniBE Contributor:

Caldelari, Reto and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Funders:

[42] Schweizerischer Nationalfonds

Language:

English

Submitter:

Volker Heussler

Date Deposited:

02 Feb 2021 14:21

Last Modified:

10 Mar 2021 12:03

Publisher DOI:

10.3389/fimmu.2020.585502

PubMed ID:

33329563

Uncontrolled Keywords:

CD8-CD4 T cells inflammation liver malaria vaccine

BORIS DOI:

10.48350/151692

URI:

https://boris.unibe.ch/id/eprint/151692

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