Short Analytical ReviewRole of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts
Section snippets
Contribution of Toll-like receptors (TLRs) to the innate immune response of the host
In recent years, the TLR family has emerged as a major group of pathogen-recognition receptors that play a central role in the induction of immune responses. Humans express at least 10 TLRs involved in the recognition of various pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), a major component of Gram-negative bacteria and detected by TLR4, as well as lipopeptides produced mainly by Gram-positive bacteria and detected by TLR2. Other interactions include those
The innate immune response to A. fumigatus
A. fumigatus is an airborne fungus. Its conidia are small enough to reach the alveoli easily during breathing. In immunocompromised patients, conidia germinate, and hyphae develop and invade the parenchyma. This leads to tissue destruction and respiratory failure characteristic of invasive pulmonary aspergillosis (IPA), a life-threatening disease with a death rate higher than 60% [5]. Mortality from IPA has increased several-fold during the last 20 year period, a finding that is explained by
Immunosuppression and TLRs
Whereas MyD88−/−, TLR2−/−, and/or TLR4−/− neutropenic mice do not survive A. fumigatus pulmonary infection, immunocompetent mice do [30], [31], [34]. Therefore, TLR2 and/or TLR4 are essential in the absence of PMN, but not in the healthy host. This suggests that TLRs expressed by PMN are not as important in vivo as other pathogen-recognition receptors expressed by PMN. One such critical pathogen-recognition receptor may be Dectin-1, a β-glucan receptor. It is expressed by PMN [35] and is
Clinical relevance and conclusion
Our understanding of how the immune system recognizes pathogens has greatly increased in recent years, due to the discovery of TLRs. They play a central role in the detection of PAMPs and in the initiation of effective innate and adaptive immune responses [1], [2], [3]. There is accumulating evidence, based on in vitro and in vivo studies, that supports a role for TLRs in A. fumigatus sensing. Several clinical reports confirm that TLRs contribute to the pathophysiology of infectious diseases
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