Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

Svoboda, Eliška; Schneider, Andrea; Sándor, Noémi; Lermann, Ulrich; Staib, Peter; Kremlitzka, Mariann; Bajtay, Zsuzsa; Barz, Dagmar; Erdei, Anna; Józsi, Mihály

doi:10.1016/j.imlet.2015.08.009

Cited by 36 publications

(40 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional way for pathogens to escape complement attack is by recruiting (i.e., hijacking ) complement inhibitors from the host, such as FH (and C4BP) [128–130]. Indeed, some pathogens mimic a host surface by capturing these soluble complement regulators or, alternatively, target and inactivate complement inhibitors with secreted proteins/proteases [48, 131]; once a given pathogen has recruited complement inhibitors on to its own surface, it is likely protected from the complement attack as if it were self . There are several examples of bacteria that can acquire FH via the presentation of specific binding proteins.…”

Section: Factor H and Immune Evasionmentioning

confidence: 99%

“…As noted above, some pathogens can escape the immune response by synthesizing and secreting soluble proteases that can target selected complement components. This is the case for Candida albicans whose aspartic protease 2 inactivates FH and the macrophage FH-receptors CR3 and CR4 [131]. In this context, it appears that the selective degradation of FH by the microbe-encoded protease helps circumvent the pro-phagocytic activity of FH (see above).…”

Section: Factor H and Immune Evasionmentioning

confidence: 99%

See 1 more Smart Citation

Complement factor H in host defense and immune evasion

Parente

Clark

Inforzato

et al. 2016

Cell. Mol. Life Sci.

162

147

View full text Add to dashboard Cite

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

show abstract

Section: Factor H and Immune Evasionmentioning

confidence: 99%

Section: Factor H and Immune Evasionmentioning

confidence: 99%

Complement factor H in host defense and immune evasion

Parente

Clark

Inforzato

et al. 2016

Cell. Mol. Life Sci.

162

147

View full text Add to dashboard Cite

show abstract

“…This appears counterproductive because cleaved FH then loses its ability to inhibit complement activation (51). However, microbes may gain advantage from a more inflammatory micro-environment (53, 54) or, because their proteases could also cleave complement factors necessary for the propagation of the cascade (55), the functional inactivation of FH may not cause significant disadvantage in complement resistance.…”

Section: Role Of Fh In Host–microbe Interactionsmentioning

confidence: 99%

“…In this non-canonical role, FH was described to act as a bridging molecule between complement receptor 3 (CR3; CD11b/CD18) and pathogens, and helping either pathogen entry into host cells or the antimicrobial response of the host cells (51, 58–62). Such scenarios were described for FH bound to S. pneumoniae, N. gonorrhoeae , and Candida albicans (58–61).…”

Section: Role Of Fh In Host–microbe Interactionsmentioning

confidence: 99%

Factor H Family Proteins in Complement Evasion of Microorganisms

Józsi

2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Human-pathogenic microbes possess various means to avoid destruction by our immune system. These include interactions with the host complement system that may facilitate pathogen entry into cells and tissues, expression of molecules that defuse the effector complement components and complexes, and acquisition of host complement inhibitors to downregulate complement activity on the surface of the pathogen. A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H (FH) from body fluids and thus hijack its host protecting function. In addition to FH, binding of FH-related (FHR) proteins was also demonstrated for several microbes. Initial studies assumed that these proteins are complement inhibitors similar to FH. However, recent evidence suggests that FHR proteins may rather enhance complement activation both directly and also by competing with the inhibitor FH for binding to certain ligands and surfaces. This mini review focuses on the role of the main alternative pathway regulator FH in host–pathogen interactions, as well as on the emerging role of the FHR proteins as enhancers of complement activation.

show abstract

“…It has been recently shown that both CR3 and CR4 function as FH receptors on monocyte-derived macrophages (28). Thus, we exposed monocytes to blocking mAbs against integrins CD11b and CD11c, followed by 24-h coincubation with FH at the monocyte to iDC early differentiation stage.…”

Section: Fh Immunomodulatory Activity Is Mediated Neither By Cr3 or Cmentioning

confidence: 99%

The Complement Inhibitor Factor H Generates an Anti-Inflammatory and Tolerogenic State in Monocyte-Derived Dendritic Cells

Olivar

Luque

Cárdenas-Brito

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

The activation of the complement system is a key initiating step in the protective innate immune-inflammatory response against injury, although it may also cause harm if left unchecked. The structurally related soluble complement inhibitors C4b-binding protein (C4BP) and factor H (FH) exert a tight regulation of the classical/lectin and alternative pathways of complement activation, respectively, attenuating the activity of the C3/C5 convertases and, consequently, avoiding serious damage to host tissues. We recently reported that the acute-phase C4BP isoform C4BP lacking the β-chain plays a pivotal role in the modulation of the adaptive immune responses. In this study, we demonstrate that FH acts in the early stages of monocyte to dendritic cell (DC) differentiation and is able to promote a distinctive tolerogenic and anti-inflammatory profile on monocyte-derived DCs (MoDCs) challenged by a proinflammatory stimulus. Accordingly, FH-treated and LPS-matured MoDCs are characterized by altered cytoarchitecture, resembling immature MoDCs, lower expression of the maturation marker CD83 and the costimulatory molecules CD40, CD80, and CD86, decreased production of key proinflammatory Th1-cytokines (IL-12, TNF-α, IFN-γ, IL-6, and IL-8), and preferential production of immunomodulatory mediators (IL-10 and TGF-β). Moreover, FH-treated MoDCs show low Ag uptake and, when challenged with LPS, display reduced CCR7 expression and chemotactic migration, impaired CD4+ T cell alloproliferation, inhibition of IFN-γ secretion by the allostimulated T cells, and, conversely, induction of CD4+CD127low/negativeCD25highFoxp3+ regulatory T cells. Thus, this novel noncanonical role of FH as an immunological brake able to directly affect the function of MoDCs in an inflammatory environment may exhibit therapeutic potential in hypersensitivity, transplantation, and autoimmunity.

show abstract

Secreted aspartic protease 2 of Candida albicans inactivates factor H and the macrophage factor H-receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18)

Cited by 36 publications

References 53 publications

Complement factor H in host defense and immune evasion

Complement factor H in host defense and immune evasion

Factor H Family Proteins in Complement Evasion of Microorganisms

The Complement Inhibitor Factor H Generates an Anti-Inflammatory and Tolerogenic State in Monocyte-Derived Dendritic Cells

Contact Info

Product

Resources

About