Aspergillus and asthma--any link?
The innate immune and acquired immune responses are not separate, parallel systems but form interdependent components of a single integrated immune response. This is nicely highlighted by an expanding database demonstrating that the innate immune response provides the acquired immune response with information about the origin of the antigen and the type of response required via pattern recognition receptors (PRRs). Aspergillus is among a growing list of allergens that can aggravate asthmatic responses. Significant pulmonary pathology is associated with Aspergillus-induced allergic and asthmatic lung disease characterized by increased Th2 cytokine generation, IgE and IgG, eosinophilia, airway hyper-responsiveness and airway remodeling. Experimental data from a model of chronic fungal asthma demonstrate that thymus associated and regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22), working via CCR4, directly impair the innate anti-fungal immune response, thereby promoting the maintenance of acquired Th2-mediated asthmatic disease. Both chemokines appear to accomplish this by regulating the expression of PRRs such as toll like receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) by immune cells. Thus, the link between Aspergillus and asthma appears to reside in the magnitude and appropriateness of the host innate immune response, and ongoing research is revealing promising targets for therapy.
Hogaboam
C M
CM
Department of Pathology, University of Michigan Medical School, Rm 5216B, Med Sci I, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA. Hogaboam@med.umich.edu
Carpenter
K J
KJ
Schuh
J M
JM
Buckland
K F
KF
D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications* / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus; D001249:Asthma / Q000382:microbiology*; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D051193:Toll-Like Receptors
D018925:Chemokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors