Pulmonary allergic responses augment interleukin-13 secretion by circulating basophils yet suppress interferon-alpha from plasmacytoid dendritic cells.
BACKGROUND
Allergic inflammatory processes may have the capacity to propagate systemically through the actions of circulating leucocytes. Consequently, basophils from allergic individuals are often 'primed', as evidenced by their hyperresponsiveness in vitro. IFN-alpha secreted predominantly by plasmacytoid dendritic cells (pDCs), suppresses basophil priming for IL-13 production in vitro.


OBJECTIVE
This study sought in vivo correlates arising during experimental allergen challenge that support an 'axis-interplay' between basophils and pDCs.


METHODS
Using segmental allergen challenge (SAC) in the lung, the immune responses of both cell types from the blood were investigated in volunteers (n=10) before and 24 h after allergen exposure. These responses were then correlated with inflammatory parameters measured in bronchoalveolar lavage fluids (BALF).


RESULTS
In the blood, SAC significantly augmented IL-13 secretion by basophils induced by IL-3 (P=0.009), yet reduced IFN-alpha secreted by pDCs stimulated with CpG (P=0.018). Both parameters were negatively correlated (P=0.0015), at least among those subjects that secreted the latter. Circulating basophil IL-13 responses further correlated with post-SAC bronchoalveolar lavage (BAL) parameters including IL-13 protein (P=0.04), basophil (P=0.051), eosinophil (P=0.0018), and total cell counts (P<0.003). Basophil and IL-13 levels in BAL correlated likewise (P=0.0002).


CONCLUSIONS
These results support a mechanism of immune regulation whereby an allergen reduces innate immune responses and IFN-alpha production by pDCs, resulting in an enhanced inflammation and basophil cytokine production at sites of allergen exposure.
Schroeder
J T
JT
The Department of Medicine, Divisions of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. schray@jhmi.edu
Bieneman
A P
AP
Chichester
K L
KL
Breslin
L
L
Xiao
H
H
Liu
M C
MC
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D001491:Basophils / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology*; D009841:Oligonucleotides / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D016207:Cytokines; D016898:Interferon-alpha; D018793:Interleukin-13; D009841:Oligonucleotides; D010940:Plant Proteins; D004247:DNA