<i>Streptococcus pyogenes</i> evades adaptive immunity through specific IgG glycan hydrolysis

Naegeli, Andreas; Bratanis, Eleni; Karlsson, Christofer; Shannon, Oonagh; Kalluru, Raja; Linder, Adam; Malmström, Johan; Collin, Mattias

doi:10.1084/jem.20190293

Cited by 30 publications

(24 citation statements)

References 74 publications

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“…This fact can be used for early diagnosis of concomitant VGL-6 infection in children with tonsillitis. The study of the properties of Ig G in streptococcal infection is important in terms of the identified opportunities to avoid the pathogen from the immune response [19].…”

Section: Discussionmentioning

confidence: 99%

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

2021

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The aim of the work is to study the indicators of cellular and humoral immune response and FAN of patients with tonsillitis in children infected with HHV-6 type. Materials and methods of research. In 72 children aged 3–15 years (mean age 8.42±1.44 years), patients with streptococcal tonsillitis of moderate severity, the levels of the main subpopulations of blood lymphocytes were determined using monoclonal antibodies by solid-phase enzyme-linked immunosorbent assay, phagocytic activity of neutrophils (FAN) using the nitrosine tetrazolium reduction test (HCT test) and serum IgA, IgM, IgG levels by radial immunodiffusion. The studies were carried out in the acute period and in the period of convalescence. Mathematical and statistical processing of the data obtained was carried out using Microsoft Excel 2003 and Statistica 6.0 programs. The significance of differences between the mean values was determined using the Student's test (t). Results. Different mechanisms of formation of pathological process at streptococcal tonsillitis at children depending on the concomitant HHV-6 type infection are revealed. In patients with mixed infection in the acute period of tonsillitis determine the signs of deficiency of the cellular immune system with the maximum deviation of CD-lymphocytes (t=3.13 vs. t=2.16 in mono-infection), the tension in the humoral link of the immune response Ig deviation (t=1.63 against t=0.91 in mono-infection) on the background of phagocytosis violation in terms of FAN deviation (t=3.22 against t=2.01 in mono-infection). By the period of convalescence, the restoration of the imbalance of specific and non-specific protection factors does not occur. Increased IgG content in the acute period is one of the features of streptococcal tonsillitis in children on the background of HHV-6t infection. Conclusions. Concomitant VGL-6 type infection in children with streptococcal tonsillitis affects the mechanisms of formation of the inflammatory process and the reactivity of patients, forming the preconditions for adverse outcomes of the disease. The obtained results can be the basis for early detection of herpes virus infection in patients with tonsillitis, will help to optimize the management of patients in different periods of the disease.

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Section: Discussionmentioning

confidence: 99%

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

2021

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“…showed that the IgG glycan hydrolase from S . pyogenes decreased phagocytic killing of bacteria due to glycan loss and reduction in complement-activation activity, and its expression increased virulence of the organism in a mouse model [ 26 ]. Glycan-dependent complement activation by antibody to PNAG is essential for protective efficacy [ 14 , 17 ], suggesting that antigens inducing neutralizing antibody to the SEE endopeptidase IgeE and the EndoSee glycan hydrolase may need to be included in an effective vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…A strangles vaccine candidate that was recently shown to reduce clinical signs of strangles in a challenge study of ponies contained antigens targeting SEE enzymes that degrade IgG or inhibit its functional activity [25]. Targeting these virulence factors could be essential, as Naegeli et al showed that the IgG glycan hydrolase from S. pyogenes decreased phagocytic killing of bacteria due to glycan loss and reduction in complement-activation activity, and its expression increased virulence of the organism in a mouse model [26]. Glycandependent complement activation by antibody to PNAG is essential for protective efficacy [14,17], suggesting that antigens inducing neutralizing antibody to the SEE endopeptidase IgeE and the EndoSee glycan hydrolase may need to be included in an effective vaccine.…”

Section: Plos Onementioning

confidence: 99%

Vaccination of yearling horses against poly-N-acetyl glucosamine fails to protect against infection with Streptococcus equi subspecies equi

et al. 2020

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Strangles is a common disease of horses with worldwide distribution caused by the bacterium Streptococcus equi subspecies equi (SEE). Although vaccines against strangles are available commercially, these products have limitations in safety and efficacy. The microbial surface antigen β 1→6 poly- N -acetylglucosamine (PNAG) is expressed by SEE. Here we show that intramuscular (IM) injection alone or a combination of IM plus intranasal (IN) immunization generated antibodies to PNAG that functioned to deposit complement and mediate opsonophagocytic killing of SEE ex vivo . However, immunization strategies targeting PNAG either by either IM only injection or a combination of IM and IN immunizations failed to protect yearling horses against infection following contact with infected horses in an experimental setting. We speculate that a protective vaccine against strangles will require additional components, such as those targeting SEE enzymes that degrade or inactivate equine IgG.

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“…IdeS hydrolyzes four subclasses of IgG, whereas EndoS specifically alters IgG Fc glycosylation [ 68 , 69 ]. Subsequently, altered IgG cannot opsonize the pathogen resulting in impaired phagocytosis and pathogen clearance by phagocytic cells.…”

Section: Major Gas Virulence Factorsmentioning

confidence: 99%

Streptococcus pyogenes (“Group A Streptococcus”), a Highly Adapted Human Pathogen—Potential Implications of Its Virulence Regulation for Epidemiology and Disease Management

Siemens

Lütticken²

2021

Pathogens

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Streptococcus pyogenes (group A streptococci; GAS) is an exclusively human pathogen. It causes a variety of suppurative and non-suppurative diseases in people of all ages worldwide. Not all can be successfully treated with antibiotics. A licensed vaccine, in spite of its global importance, is not yet available. GAS express an arsenal of virulence factors responsible for pathological immune reactions. The transcription of all these virulence factors is under the control of three types of virulence-related regulators: (i) two-component systems (TCS), (ii) stand-alone regulators, and (iii) non-coding RNAs. This review summarizes major TCS and stand-alone transcriptional regulatory systems, which are directly associated with virulence control. It is suggested that this treasure of knowledge on the genetics of virulence regulation should be better harnessed for new therapies and prevention methods for GAS infections, thereby changing its global epidemiology for the better.

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Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

Abstract: EndoS from Streptococcus pyogenes hydrolyzes the functionally important glycan on the Fc portion of IgG during infections in humans. In mice with IgG mediated immunity against the M1 protein on the bacteria, EndoS is a virulence factor.

Cited by 30 publications

References 74 publications

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

Vaccination of yearling horses against poly-N-acetyl glucosamine fails to protect against infection with Streptococcus equi subspecies equi

Streptococcus pyogenes (“Group A Streptococcus”), a Highly Adapted Human Pathogen—Potential Implications of Its Virulence Regulation for Epidemiology and Disease Management

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