The role of innate immunity in asthma: leads and lessons from mouse models.
According to the Hygiene Hypothesis, respiratory infections should protect individuals from allergic diseases including asthma, but epidemiologic data on the role of infections or exposure to microbial compounds in asthma are contradictory. Meanwhile, a number of murine models of airway sensitization are available facilitating the elucidation of pathways involved in asthma pathogenesis. Such studies have linked antigen presentation by activated pulmonary dendritic cells (DCs) with airway sensitization. Toll-like receptors (TLRs), which play a major role in innate immunity by sensing various microbial compounds, are expressed on DCs, as well as on mast cells (MCs). Activation of TLRs by administration of specific bacterial ligands, in particular lipopolysaccharide, can augment airway sensitization in mice, and there is evidence that this process involves TLR-dependent activation of DCs. Intriguingly, viral infection has been shown to increase airway inflammation in a murine asthma model via activation of DCs as well. TLR-4-dependent stimulation of MCs may also play a role in allergic sensitization in mice, and in vitro studies in murine cells show that ligation of TLRs expressed on MCs enhances degranulation. Therefore, evidence obtained from studies on mice indicates that innate immune responses may promote, rather than protect from, the development as well as the exacerbation of asthma.
Schröder
N W J
NW
Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité- Universitätsmedizin Berlin, Berlin, Germany.
Maurer
M
M
D000818:Animals; D001249:Asthma / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D008407:Mast Cells / Q000276:immunology; D051379:Mice / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D051193:Toll-Like Receptors