Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

Amélie Savers; Orhan Rasid; Marianna Parlato; Matthias Brock; Gregory Jouvion; Bernhard Ryffel; Jean-Marc Cavaillon; Gerard Eberl; Oumaïma Ibrahim-Granet

doi:10.1371/journal.pone.0153829

Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

PLoS One. 2016 Apr 14;11(4):e0153829. doi: 10.1371/journal.pone.0153829. eCollection 2016.

Authors

Amélie Savers^{1

2}, Orhan Rasid¹, Marianna Parlato³, Matthias Brock², Gregory Jouvion⁴, Bernhard Ryffel⁵, Jean-Marc Cavaillon¹, Gerard Eberl⁶, Oumaïma Ibrahim-Granet¹

Affiliations

¹ Institut Pasteur, Unité Cytokines & Inflammation, Paris, France.
² Fungal Genetics and Biology, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
³ INSERM UMR S1163 -Institut Imagine, Laboratoire d'Immunité Intestinale, Paris, France.
⁴ Institut Pasteur, Unité Histopathologie Humaine et Modèles Animaux, Paris, France.
⁵ INSERM, UMR 7355, Immunologie Moléculaire, Institut de Transgénose, Université d'Orléans et Centre National de la Recherche Scientifique, Orléans, France.
⁶ Institut Pasteur, Lymphoid Tissue Development Unit, Paris, France.

Abstract

Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aspergillosis / immunology*
Aspergillosis / microbiology
Aspergillus fumigatus / immunology*
Aspergillus fumigatus / physiology
Bone Marrow / immunology
Bone Marrow / metabolism
Bone Marrow / microbiology
Chemokines / immunology
Chemokines / metabolism
Cytokines / immunology
Cytokines / metabolism
Disease Resistance / immunology
Flow Cytometry
Host-Pathogen Interactions / immunology
Lectins, C-Type / immunology
Lectins, C-Type / metabolism
Lung / immunology
Lung / metabolism
Lung / microbiology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Phagocytes / immunology*
Phagocytes / metabolism
Phagocytes / microbiology
Receptors, Interleukin-8B / immunology
Receptors, Interleukin-8B / metabolism
Spores, Fungal / immunology*
Spores, Fungal / physiology

Substances

Chemokines
Cytokines
Lectins, C-Type
Receptors, Interleukin-8B
dectin 1

Grants and funding

This work was supported by funding from Institut Pasteur PTR 468 to OIG and AS, and the Transregio 124 “FungiNet” project A3 to AS and MB.