Activation of the complement system by pathogenic fungi

Abstract

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus

“…To examine this, we used an antibody against C4d, a sensitive and reliable marker for complement deposition 13. Since pathogenic fungi have been reported to be potent inducers of complement activation cascade,14 pulmonary tissue from a patient with Aspergillus infection was tested in parallel as positive control (figure 4G). We found that no measurable C4d signal was obtained from the lungs of patients 1 and 2 (figure 4D, E) similar to normal control (figure 4F).…”

Role of Mannose‐Binding Lectin in the Innate Defense againstCandida albicans:Enhancement of Complement Activation, but Lack of Opsonic Function, in Phagocytosis by Human Dendritic Cells

“…albicans activates both the alternative and the classical pathway of complement [48], and the complement system is important in the resistance against disseminated and cutaneous candidiasis [49]. Antibodies protective against candidiasis require efficient deposition of complement on the fungal surface [50].…”

Enhanced Sensitivity of Tumor Necrosis Factor/Lymphotoxin‐α–Deficient Mice toCryptococcus neoformansInfection despite Increased Levels of Nitrite/Nitrate, Interferon‐γ, and Interleukin‐12

“…The host's response to C. neoformans infection is a complex interplay between cytokine regulation and cellular and humoral immunity, with the complement system playing a major role. The activation of the alternative pathway by encapsulated C. neoformans not only favors its opsonization by phagocytic cells [15][16][17] but also enhances the cytokine production induced by this fungus [18,19].…”