sTLR2 (B) or sTLR4 (C) was coated onto microtiter wells and incubated with the indicated concentrations of MBL, respectively. could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4. == Conclusions/Significance == Our study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions (+)-Catechin (hydrate) by modifyingC. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation ofC. albicans-induced cellular responses. == Introduction == Candida albicans(C. albicans) is, a dimorphic fungus, the most common pathogen of humans among fungi and a component of the normal microflora of skin, mucosa and alimentary tract of the healthy host[1]. However, when immune defenses are compromised or the normal microflora balance is disrupted,Candidatransforms itself into an opportunistic pathogenic killer. Indeed, dissemination ofCandidais the leading cause of invasive fungal disease in diabetics, premature infants, and surgical patients and of oropharyngeal disease in AIDS patients[2],[3],[4].C. albicansexhibits the ability to grow in a variety of reversible morphological forms [yeast forms (Y), pseudohyphal forms, and hyphal forms (H)] in response to various environmental signals[5]. The ability ofC. albicansto switch its mode of growth has been shown to be required for the pathogenicity of this fungus[6]. Hyphae formation from yeast cells is a virulence trait enabling this fungus to invade host tissues[7]. The innate immune system, including the complement system, acts as a first line of defense against pathogens. Mannan-binding lectin (MBL), a member of the collectin family in the C-type lectin superfamily, is an important serum component in innate immunity[8],[9]. MBL recognizes a wide range of infectious agents, such as yeasts, bacteria, viruses, parasites, etc. via its C-terminal carbohydrate-recognition domains (CRDs). On binding (+)-Catechin (hydrate) to pathogens, MBL activates the complement system in an antibody- and C1-independent process involving MBL connected serine proteases, thereby facilitating pathogen removal[10]. MBL also facilitates phagocytosis of cellular debris and may consequently prevent autoimmunity[11],[12]. It is well known that pattern-recognition receptors, such as toll-like receptors (TLRs), perform a key part as they can identify pathogens and activate the acquired immune response[13],[14]. Activating probably the most TLRs prospects to recruitment of MyD88, which can interact with IL-1 receptor-associated kinase, leading to initiation of a signal transduction cascade culminating in nuclear translocation of nuclear factor-B (NF-B) family members and then modified the gene expressions, such as IL-8, TNF- and (+)-Catechin (hydrate) additional cytokines that play important part in immune response and swelling[15],[16]. Studies possess demonstrated the crucial involvement of TLRs in the acknowledgement of fungal pathogens such asC. albicans, although less is known concerning the function of these receptors followingCandidainfection[17],[18]. Among the TLR family, mainly TLR2 and TLR4, are involved in the sponsor connection withC. albicansand play a significant role in the development of sponsor immune reactions during candidiasis[19]. The host’s response to illness is most likely due TSPAN31 to the different acknowledgement/activation patterns of these receptors and the launch of several proinflammatory cytokines and chemokines[15],[20]. (+)-Catechin (hydrate) The part of MBL like a modulator of illness appears to be (+)-Catechin (hydrate) complex and, accordingly, its mechanism of action remains incompletely characterized. Recently, we have proved that MBL can regulate dendritic cell (DC) maturation and cytokine production induced by lipopolysaccharide (LPS)[21], and, MBL can bind to TLR4 directly, and suppress LPS-induced inflammatory cytokine secretion from THP-1 cells[22]. It has also been reported that MBL can facilitate opsonophagocytosis.
sTLR2 (B) or sTLR4 (C) was coated onto microtiter wells and incubated with the indicated concentrations of MBL, respectively
