Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity

Ursula Smole; Naina Gour; Jordan Phelan; Gerhard Hofer; Cordula Köhler; Bernhard Kratzer; Peter A Tauber; Xiao Xiao; Nu Yao; Jan Dvorak; Luis Caraballo; Leonardo Puerta; Sandra Rosskopf; Jamila Chakir; Ernst Malle; Andrew P Lane; Winfried F Pickl; Stephane Lajoie; Marsha Wills-Karp

doi:10.1038/s41590-020-0698-1

Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity

Nat Immunol. 2020 Jul;21(7):756-765. doi: 10.1038/s41590-020-0698-1. Epub 2020 Jun 22.

Authors

Ursula Smole^{1

2}, Naina Gour³, Jordan Phelan³, Gerhard Hofer⁴, Cordula Köhler⁵, Bernhard Kratzer⁵, Peter A Tauber⁵, Xiao Xiao³, Nu Yao³, Jan Dvorak^{6

7

8}, Luis Caraballo⁹, Leonardo Puerta⁹, Sandra Rosskopf⁵, Jamila Chakir¹⁰, Ernst Malle¹¹, Andrew P Lane¹², Winfried F Pickl⁵, Stephane Lajoie^{3

12}, Marsha Wills-Karp¹³

Affiliations

¹ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [email protected].
² Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. [email protected].
³ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, Graz, Austria.
⁵ Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁶ Department of Zoology and Fisheries, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences, Prague, Czech Republic.
⁷ Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
⁸ Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic.
⁹ Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
¹⁰ Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, Canada.
¹¹ Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.
¹² Division of Rhinology and Sinus Surgery, Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹³ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [email protected].

Abstract

The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13). The interaction between mite FABPs and SAA1 activated the SAA1-binding receptor, formyl peptide receptor 2 (FPR2), which drove the epithelial release of the type-2-promoting cytokine interleukin (IL)-33 in a SAA1-dependent manner. Importantly, the SAA1-FPR2-IL-33 axis was upregulated in nasal epithelial cells from patients with chronic rhinosinusitis. These findings identify an unrecognized role for SAA1 as a soluble pattern recognition receptor for conserved FABPs found in common mite allergens that initiate type 2 immunity at mucosal surfaces.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Allergens / immunology
Animals
Antigens, Dermatophagoides / immunology
Asthma / immunology*
Asthma / pathology
Cells, Cultured
Disease Models, Animal
Epithelial Cells
Fatty Acid-Binding Proteins / immunology
Female
Humans
Immunity, Humoral
Immunity, Innate
Interleukin-33 / metabolism
Lung / cytology
Lung / immunology
Lung / pathology
Male
Mice
Mice, Knockout
Middle Aged
Primary Cell Culture
Receptors, Formyl Peptide / metabolism
Receptors, Lipoxin / metabolism
Respiratory Mucosa / immunology
Respiratory Mucosa / metabolism
Rhinitis, Allergic / immunology*
Rhinitis, Allergic / pathology
Serum Amyloid A Protein / genetics
Serum Amyloid A Protein / metabolism*
Signal Transduction / immunology*
Up-Regulation
Young Adult

Substances

Allergens
Antigens, Dermatophagoides
FPR2 protein, human
Fatty Acid-Binding Proteins
IL33 protein, human
Il33 protein, mouse
Interleukin-33
Receptors, Formyl Peptide
Receptors, Lipoxin
SAA1 protein, human
Saa2 protein, mouse
Serum Amyloid A Protein
formyl peptide receptor 2, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding