Publikationsdatenbank

TLR9 signalling inhibits Plasmodium liver infection by macrophage activation (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Kordes, Maximilian

Ormond, Louise

Rausch, Sebastian (WE 6)

Matuschewski, Kai

Hafalla, Julius Clemence R.

Quelle

European journal of immunology : basic, clinical, translational

Bandzählung: 52

Heftzählung: 2

Seiten: 270 – 284

ISSN: 1521-4141

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1002/eji.202149224

DOI: 10.1002/eji.202149224

Pubmed: 34773640

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Recognition of pathogen-associated molecular patterns (PAMPs) through Toll-like receptors (TLRs) plays a pivotal role in first-line pathogen defence. TLRs are likely also triggered during a Plasmodium infection in vivo by parasite-derived components. However, the contribution of innate responses to liver infection and to the subsequent clinical outcome of a blood infection is not well understood. To assess the potential effects of enhanced TLR-signalling on Plasmodium infection, we systematically examined the effect of agonist-primed immune responses to sporozoite inoculation in the P. berghei/ C57Bl/6 murine malaria model. We could identify distinct stage-specific effects on the course of infection after stimulation with two out of four TLR-ligands tested. Priming with a TLR9 agonist induced killing of pre-erythrocytic stages in the liver that depended on macrophages and the expression of iNOS. These factors have previously not been recognised as antigen-independent effector mechanisms against Plasmodium liver-stages. Priming with TLR4 and -9 agonists also translated into blood stage-specific protection against experimental cerebral malaria (ECM). These insights are relevant to the activation of TLR signalling pathways by adjuvant systems of anti-malaria vaccine strategies. The protective role of TLR4-activation against ECM might also explain some unexpected clinical effects observed with pre-erythrocytic vaccine approaches. This article is protected by copyright. All rights reserved.