Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

doi:10.3389/fmicb.2017.00868

Cited by 20 publications

(17 citation statements)

References 59 publications

(66 reference statements)

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“…Upon infection, the complement cascade also activates and plays a role in combating pathogens via enhancing chemotaxis, phagocytosis, or T and B cell differentiation (23). Pathogenic species have adopted several strategies to evade complement attack (24). In particular, C.…”

Section: Introductionmentioning

confidence: 99%

Functional Characterization of Secreted Aspartyl Proteases in Candida parapsilosis

Singh

Németh

Papp

et al. 2019

mSphere

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Candida parapsilosis is an emerging non-albicans Candida species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establishment and progression of disease. Although secreted aspartyl proteases (Sap) are critical for Candida albicans pathogenicity, their role in C. parapsilosis is poorly elucidated. In the present study, we aimed to examine the contribution of C. parapsilosis SAPP genes SAPP1, SAPP2, and SAPP3 to the virulence of the species. Our results indicate that SAPP1 and SAPP2, but not SAPP3, influence adhesion, host cell damage, phagosome-lysosome maturation, phagocytosis, killing capacity, and cytokine secretion by human peripheral blood-derived macrophages. Purified Sapp1p and Sapp2p were also shown to efficiently cleave host complement component 3b (C3b) and C4b proteins and complement regulator factor H. Additionally, Sapp2p was able to cleave factor H-related protein 5 (FHR-5). Altogether, these data demonstrate the diverse, significant contributions that SAPP1 and SAPP2 make to the establishment and progression of disease by C. parapsilosis through enabling the attachment of the yeast cells to mammalian cells and modulating macrophage biology and disruption of the complement cascade. IMPORTANCE Aspartyl proteases are present in various organisms and, among virulent species, are considered major virulence factors. Host tissue and cell damage, hijacking of immune responses, and hiding from innate immune cells are the most common behaviors of fungal secreted proteases enabling pathogen survival and invasion. C. parapsilosis, an opportunistic human-pathogenic fungus mainly threatening low-birth weight neonates and children, possesses three SAPP protein-encoding genes that could contribute to the invasiveness of the species. Our results suggest that SAPP1 and SAPP2, but not SAPP3, influence host evasion by regulating cell damage, phagocytosis, phagosome-lysosome maturation, killing, and cytokine secretion. Furthermore, SAPP1 and SAPP2 also effectively contribute to complement evasion.

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Section: Introductionmentioning

confidence: 99%

Functional Characterization of Secreted Aspartyl Proteases in Candida parapsilosis

Singh

Németh

Papp

et al. 2019

mSphere

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“… 54 C1q is critical for apoptotic cell removal, in addition to its role in the initiation of the classical pathway of complement activation, 55 while C3a and C5a are potent proinflammatory chemokines. 56 There are 3 well-characterized pathways of complement activation: the classical pathway is mostly triggered by the binding of C1q to antigen-antibody complexes; the lectin pathway by binding of pattern recognition molecules to surface carbohydrates involving mannose-binding lectin-associated serine proteases that catalyze C4 and C2 cleavage of the classical cascade; 57 and finally, the alternative pathway which is constitutively active at a low level. Regardless of how the complement cascade is activated, it results in the formation of C3 and C5 convertase, inflammatory chemokines, and assembly of the membrane attack complex (MAC) which punctures cell membranes causing cell lysis and efflux of cell content.…”

Section: Reviewmentioning

confidence: 99%

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review

McFarlane

Bitzan

Broome

et al. 2021

Can J Kidney Health Dis

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Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli–induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. Sources of information: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted with PubMed or based on the prior knowledge of the authors. Methods: This review is the result of a consultation process that reflects the consensus of experts from Canada, the United States, and the United Arab Emirates. The members represent individuals who are clinicians, researchers, and teachers in pediatric and adult medicine from the fields of hematology, nephrology, and laboratory medicine. Authors, through an iterative review process identified and synthesized information from relevant published studies. Key findings: Thrombotic thrombocytopenic purpura occurs in the setting of insufficient activity of the von Willebrand factor protease known as ADAMTS13. Shiga toxin-producing Escherichia coli–induced hemolytic uremic syndrome, also known as “typical” HUS, is caused by gastrointestinal infections with bacteria that produce Shiga toxin (initially called verocytotoxin). A variety of clinical conditions or drug exposures can trigger TMA. Finally, aHUS occurs in the setting of inherited or acquired abnormalities in the alternative complement pathway leading to dysregulated complement activation, often following a triggering event such as an infection. It is possible to break the process of etiological diagnosis of TMA into 2 distinct steps. The first covers the initial presentation and diagnostic workup, including the processes of identifying the presence of TMA, appropriate initial tests and referrals, and empiric treatments when appropriate. The second step involves confirming the etiological diagnosis and moving to definitive treatment. For many forms of TMA, the ultimate response to therapies and the outcome of the patient depends on the rapid and accurate identification of the presence of TMA and then a standardized approach to seeking the etiological diagnosis. We present a structured approach to identifying the presence of TMA and steps to identifying the etiology including standardized lab panels. We emphasize the importance of early consultation with appropriate specialists in hematology and nephrology, as well as identification of whether the patient requires plasma exchange. Clinicians should consider appropriate empiric therapies while following the steps we have recommended toward definitive etiologic diagnosis and management of the TMA. Limitations: The evidence base for our recommendations consists of small clinical studies, case reports, and case series. They are generally not controlled or randomized and do not lend themselves to a stricter guideline-based methodology or a Grading of Recommendations Assessment, Development and Evaluation (GRADE)-based approach.

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“…The lectin pathway of complement activation is induced by pattern recognition molecules mannosebinding lectin (MBL), ficolins (ficolin-1 to 3) or collectin-10/-11 that all sense carbohydrate ligands at microbial surfaces [39]. The importance of MBLs in killing of NTHi via the lectin pathway has not been fully evaluated, but a series of clinical reports exist.…”

Section: Haemophilus-dependent Interference With the Classical And Lementioning

confidence: 99%

Complement evasion by the human respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis

Riesbeck

2020

FEBS Letters

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All infective bacterial species need to conquer the innate immune system in order to colonize and survive in their hosts. The human respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis are no exceptions and have developed sophisticated mechanisms to evade complement-mediated killing. Both bacterial species carry lipooligosaccharides preventing complement attacks and attract and utilize host complement regulators C4b binding protein and factor H to inhibit the classical and alternative pathways of complement activation, respectively. In addition, the regulator of the terminal pathway of complement activation, vitronectin, is hijacked by both bacteria. An array of different outer membrane proteins (OMP) in H. influenzae and M. catarrhalis simultaneously binds complement regulators, but also plasminogen. Several of the bacterial complement-binding proteins are important adhesins and contain highly conserved regions for interactions with the host. Thus, some of the OMP are viable targets for new therapeutics, including vaccines aimed at preventing respiratory tract diseases such as otitis media in children and exacerbations in patients suffering from chronic obstructive pulmonary disease.

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Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

Cited by 20 publications

References 59 publications

Functional Characterization of Secreted Aspartyl Proteases in Candida parapsilosis

Functional Characterization of Secreted Aspartyl Proteases in Candida parapsilosis

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review

Complement evasion by the human respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis

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