Interferon-mediated innate immune responses against malaria parasite liver stages.

Abstract

Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by these infection-engendered innate responses. This suppression was abrogated in mice deficient in IFNγ, the type I IFN α/β receptor (IFNAR), and interferon regulatory factor 3. Natural killer and CD49b(+)CD3(+) natural killer T (NKT) cells increased in the liver after a primary infection, and CD1d-restricted NKT cells, which secrete IFNγ, were critical in reducing liver-stage burden of a secondary infection. Lack of IFNAR signaling abrogated the increase in NKT cell numbers in the liver, showing a link between type I IFN signaling, cell recruitment, and subsequent parasite elimination. Our findings demonstrate innate immune sensing of malaria parasite liver-stage infection and that the ensuing innate responses can eliminate the parasite.

• Authors: Jessica L Miller, Brandon K Sack, Michael Baldwin, Ashley M Vaughan, Stefan H I Kappe
• Journal: Cell reports (Cell Rep) Vol. 7 Issue 2 Pg. 436-447 (Apr 24 2014) ISSN: 2211-1247 [Electronic] United States
• PMID: 24703850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD1d
• CD1d antigen, mouse
• Integrin alpha2
• Interferon Regulatory Factor-3
• Interferon Type I
• Irf3 protein, mouse
• Receptor, Interferon alpha-beta
• Interferon-gamma

Topics

• Animals
• Antigens, CD1d (genetics, metabolism)
• Female
• Immunity, Innate
• Integrin alpha2 (genetics, metabolism)
• Interferon Regulatory Factor-3 (genetics, metabolism)
• Interferon Type I (genetics, metabolism)
• Interferon-gamma (genetics, metabolism)
• Killer Cells, Natural (immunology, metabolism)
• Liver (immunology, parasitology)
• Malaria (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Plasmodium (immunology, pathogenicity)
• Receptor, Interferon alpha-beta (genetics, metabolism)
• Sporozoites (immunology)