Another recent study found no ficolin-2 by proteomic in BAL samples from infected patients (n?=?10) compared to controls, suggesting ficolin-2 may have been consumed [41]. better grasp the complexity of humoral immune interaction with is an ubiquitous saprophytic mold, and it reproduces asexually forming spores (called conidia) [1]. When inhaled, these airborne conidia are rapidly cleared by the mucociliary function and resident macrophages without stimulating any undue immune response [2]. However, in certain patient populations with immunosuppression and underlying lung disease, this fungus can cause acute and/or chronic conditions, collectively called aspergillosis, with three main entities [2]. Invasive pulmonary aspergillosis (IPA) IRAK inhibitor 6 (IRAK-IN-6) occurs in severely immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients, with neutropenia or receiving heavy chemotherapy and/or corticosteroids for specific hematological malignancies and solid tumors [3]. Recently, IPA has been increasingly described in critically ill patients with viral acute respiratory distress syndrome [4, 5]. Chronic pulmonary aspergillosis (CPA) is responsible for various clinical presentations ranging from asymptomatic aspergilloma in patients with preexisting lung cavities (e.g., tuberculosis sequalae) to cavitary forms with an important clinical impact on general status in patients with underlying lung diseases [6]. CPA may evolve into lung fibrosis if untreated and/or subacute invasive forms when immunosuppressive factors are added [6]. Finally, hypersensitivity to a critically risky pathogen in the recent fungal priority pathogen list [8]. Understanding aspergillosis and its spectrum of diseases relies, therefore, mainly on understanding host immunity, whether insufficient or exacerbated. The host immune system is composed of both cellular and humoral components. While the cellular immunity (involving neutrophils, macrophages, dendritic cells and epithelial cells to some extent) has been extensively studied [9, 10], the humoral immune function has been understudied. Indeed, adequate cellular response may not occur in the absence of humoral components. In general, humoral components facilitate microbial phagocytosis by coating (opsonizing) pathogens, prevent pathogen entry into non-immune cells by neutralizing them, and may act as anaphylatoxins recruiting immune cells. Furthermore, humoral components can have a direct inhibiting impact on microbial growth and metabolism, up to direct killing. Before exposing host-fungal interactions involving humoral immunity, it is necessary to understand the complex life cycle of cell IRAK inhibitor 6 (IRAK-IN-6) wall constitutes the first interface between host immune components and the fungus [13]. This review intends to summarize the available Rabbit Polyclonal to IRF4 knowledge on major players of humoral immunity against pathogenesis. The Major Players of Humoral Immunity AgainstA. fumigatusimmunityand enhances neutrophil motility and their extravasation into the airway at the site of infection[41, 75]Histatin-5AMPNANAInhibition of hyphae metabolism[57]HistonesAMPNANAMajor components of neutrophil extracellular traps. Inhibition of hyphae metabolism[56]LactoferrinAMPNA in BALIron depletion. Inhibition of germination[41, 56, 57]LysozymeAMPNANAInhibition of hyphae metabolism[56, 59, 60]MASP-1/3Complement systemNANARecruit ficolin-3 to activate complement and facilitate phagocytosis[28]MASP-2Complement systemNA in BALTo be studied[41]MBLComplement system Collectin rodA (conidia) Galactomannan (hyphae) in cornea in serum PRR binding to and activating complement system through the lectin-pathway[36, 48, 128]PTX-3APPNA in serum and BALOpsonization promoting phagocytosis and killing by neutrophils[74]SAPAPPNA?=?in serum in BAL Activates complement and enhances phagocytosis by neutrophils[73]SP-ACollectinNA in BALOpsonization, phagocytosis, dampening Th2 response[53]SP-DCollectinMelanin (conidia) Galactomannan GAG (hyphae) in BALOpsonization, phagocytosis, triggers pro-inflammatory response, fungistatic effect[41, 48, 49]UbiquicidinAMPNANAInhibition of hyphae metabolism[57] Open in a separate window antimicrobial peptide, acute phase protein, bronchoalveolar lavage, central nervous system, galactosaminogalactan, mannose binding lectin, GalNAc N-acetyl galactosamine, NA not assessed to the best of our knowledge, PRR pattern recognition receptor The Complement System The complement system is composed of several components. Activation of the complement cascade occurs through three major routes: classical, alternative and lectin pathways. The final outcome of these molecular cascades is the formation of the Membrane Attack Complex (MAC), being inserted in the microbial membrane leading to microbial lysis. However, the thick cell wall of prevents MAC formation [14, 15]. Depending on the fungal morphotype the complement pathways will be activated. Dormant conidia, which are superficially covered by rodlet and melanin pigment layers, IRAK inhibitor 6 (IRAK-IN-6) trigger alternative pathway while the exposure of cell wall polysaccharides as the conidia germinate progressively triggers the classical/lectin pathway (Fig.?1) [16, 17, 18]. Many steps of the complement cascade before MAC IRAK inhibitor 6 (IRAK-IN-6) IRAK inhibitor 6 (IRAK-IN-6) formation represent central tools in anti-host defense, especially in recruiting neutrophils [16]. Mice deficient for complement components (e.g. C3, C5, C1q) present a higher mortality rate and more?severe pulmonary aspergillosis [15, 19, 20, 21]. Recognition by the complement system and activation of the cascade seems to interfere with fungal dissemination, supported by the fact that the level of complement.