Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions

Autor: Lindsay D Christian, Pearl M. Swe, Kadaba S. Sriprakash, Katja Fischer, H. Lu
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Complement Inhibitors
Physiology
Ectoparasitic Infections
Complement System
Sarcoptes scabiei
medicine.disease_cause
Pathology and Laboratory Medicine
Biochemistry
Complement inhibitor
Scabies
0302 clinical medicine
Immune Physiology
Medicine and Health Sciences
Enzyme-Linked Immunoassays
Complement Activation
Mites
Immune System Proteins
lcsh:Public aspects of medicine
Opsonin Proteins
3. Good health
Body Fluids
Bacterial Pathogens
Infectious Diseases
Blood
Pyoderma
Medical Microbiology
Anatomy
Pathogens
Research Article
Neglected Tropical Diseases
lcsh:Arctic medicine. Tropical medicine
Arthropoda
lcsh:RC955-962
Streptococcus pyogenes
Immunology
Sexually Transmitted Diseases
Biology
Research and Analysis Methods
Microbiology
03 medical and health sciences
Immunity
medicine
Parasitic Diseases
Animals
Humans
Immunologic Factors
Anaphylatoxin
Immunoassays
Microbial Pathogens
Innate immune system
Microbial Viability
Public Health
Environmental and Occupational Health
Organisms
Biology and Life Sciences
Proteins
lcsh:RA1-1270
Complement System Proteins
medicine.disease
biology.organism_classification
Tropical Diseases
Invertebrates
Complement system
030104 developmental biology
Complement Inactivating Agents
Immune System
Immunologic Techniques
030215 immunology
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005437 (2017)
ISSN: 1935-2735
1935-2727
Popis: Background On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently serious illness due to invasion by opportunistic bacteria. The health burden due to complicated scabies causing cellulitis, bacteraemia and sepsis, heart and kidney diseases in resource-poor communities is extreme. Co-infections of group A streptococcus (GAS) and scabies mites is a common phenomenon in the tropics. Both pathogens produce multiple complement inhibitors to overcome the host innate defence. We investigated the relative role of classical (CP), lectin (LP) and alternative pathways (AP) towards a pyodermic GAS isolate 88/30 in the presence of a scabies mite complement inhibitor, SMSB4. Methodology/Principal findings Opsonophagocytosis assays in fresh blood showed baseline immunity towards GAS. The role of innate immunity was investigated by deposition of the first complement components of each pathway, specifically C1q, FB and MBL from normal human serum on GAS. C1q deposition was the highest followed by FB deposition while MBL deposition was undetectable, suggesting that CP and AP may be mainly activated by GAS. We confirmed this result using sera depleted of either C1q or FB, and serum deficient in MBL. Recombinant SMSB4 was produced and purified from Pichia pastoris. SMSB4 reduced the baseline immunity against GAS by decreasing the formation of CP- and AP-C3 convertases, subsequently affecting opsonisation and the release of anaphylatoxin. Conclusions/Significance Our results indicate that the complement-inhibitory function of SMSB4 promotes the survival of GAS in vitro and inferably in the microenvironment of the mite-infested skin. Understanding the tripartite interactions between host, parasite and microbial pathogens at a molecular level may serve as a basis to develop improved intervention strategies targeting scabies and associated bacterial infections.
Author summary The molecular mechanisms that underpin the link between scabies and bacterial pathogens were unknown. We proposed that scabies mites play a role in the establishment, proliferation and transmission of opportunistic pathogens. We investigated here the synergy between mites and one of the most recognised mite associated pathogens, Streptococcus pyogenes. As part of the innate immune response mammals have a pre-programmed ability to recognise and immediately act against substances derived from fungal and bacterial microorganisms. This is mediated through a sequential biochemical cascade involving over 30 different proteins (complement system) which as a result of signal amplification triggers a rapid killing response. The complement cascade produces peptides that attract immune cells, increases vascular permeability, coats (opsonises) the surfaces of a pathogen, marking it for destruction, and directly disrupts foreign plasma membranes. To prevent complement mediated damage of their gut cells, scabies mites secrete several classes of complement inhibiting proteins into the mite gut and excrete them into the epidermal mite burrows. Furthermore, these inhibitors also provide protection for S. pyogenes. We verified here specifically the impact of the mite complement inhibitor SMSB4, to identify the molecular mechanisms behind the long recognised tendency of S. pyogenes to infect mite-induced skin lesions.
Databáze: OpenAIRE
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