The cleavage specificity of an IgA1 protease from<i>Haemophilus influenzae</i>

Mistry, Dippica; Stockley, Robert A.

doi:10.4161/viru.2.2.15401

Cited by 16 publications

(14 citation statements)

References 21 publications

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“…IgA protease was found in the A. paragallinarum genome, suggesting that this specie may be able to hydrolyze chicken IgA-like inmunoglobulins. IgA proteases were reported in related species as H. influenzae [23], Neisseria meningitidis [24]. This protease is known to cleave host secreted IgA immunoglobulin enabling to circumvent host mucosal defense mechanisms; enhancing the ability to infect respiratory tract [25].…”

Section: Discussionmentioning

confidence: 99%

Genome sequence and comparative analysis of Avibacterium paragallinarum

Requena

Chumbe²,

Torres³

et al. 2013

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Background: Avibacterium paragallinarum, the causative agent of infectious coryza, is a highly contagious respiratory acute disease of poultry, which affects commercial chickens, laying hens and broilers worldwide. Methodology: In this study, we performed the whole genome sequencing, assembly and annotation of a Peruvian isolate of A. paragallinarum. Genome was sequenced in a 454 GS FLX Titanium system. De novo assembly was performed and annotation was completed with GS De Novo Assembler 2.6 using the H. influenzae str. F3031 gene model. Manual curation of the genome was performed with Artemis. Putative function of genes was predicted with Blast2GO. Virulence factors were identified by comparison with the Virulence Factor Database. Results: The genome obtained has a length of 2.47 Mb with 40.66% of GC content. Seventy five large contigs (>500 nt) were obtained, which comprised 1,204 predicted genes. All the contigs are available in Genbank [GenBank: PRJNA64665]. A total of 103 virulence factors, reported in the Virulence Factor Database, were found in A. paragallinarum. Forty four of them are present in 7 species of Haemophilus, which are related with pathogenesis, virulence and host immune system evasion. A tetracycline-resistance associated transposon (Tn10), was found in A. paragallinarum, possibly acting as a defense mechanism. Discussion and conclusion: The availability of A. paragallinarum genome represents an important source of information for the development of diagnostic tests, genotyping, and novel antigens for potential vaccines against infectious coryza. Identification of virulence factors contributes to better understanding the pathogenesis, and planning efforts for prevention and control of the disease.

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Section: Discussionmentioning

confidence: 99%

Genome sequence and comparative analysis of Avibacterium paragallinarum

Requena

Chumbe²,

Torres³

et al. 2013

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“…Since previous studies have indicated SIgA may be degraded by bacterial or host proteases (18)(19)(20)(21)(22)(23)(24), we evaluated whether SIgA is degraded by non-typeable Haemophilus influenzae (NTHi), the most common bacterium isolated from the lungs of COPD patients (31), or sputum-derived human neutrophil elastase (HNE) in vitro. We incubated SIgA derived from human colostrum with conditioned media from NTHi 1479 (a clinical isolate from a COPD patient) or with HNE and performed western blots for the IgA heavy chain and the secretory component.…”

Section: Resultsmentioning

confidence: 99%

Secretory cells are the primary source of pIgR in small airways

Blackburn

Schaff

Gutor

et al. 2021

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BackgroundLoss of secretory immunoglobulin A (SIgA) is common in COPD small airways and likely contributes to disease progression. We hypothesized loss of SIgA results from reduced expression of pIgR, a chaperone protein needed for SIgA transcytosis, in the COPD small airway epithelium.MethodspIgR-expressing cells were defined and quantified at single-cell resolution in human airways using RNA in-situ hybridization, immunostaining, and single-cell RNA sequencing. Complementary studies in mice utilized immunostaining, primary murine tracheal epithelial cell (MTEC) culture, and transgenic mice with secretory or ciliated cell-specific knockout of pIgR. SIgA degradation by human neutrophil elastase or secreted bacterial proteases from non-typeable Haemophilus influenzae (NTHi) was evaluated in vitro.ResultsWe found that secretory cells are the predominant cell type responsible for pIgR expression in human and murine airways. Loss of SIgA in small airways was not associated with a reduction in secretory cells but rather a reduction in pIgR protein expression despite intact PIGR mRNA expression. Neutrophil elastase and NTHi-secreted proteases are both capable of degrading SIgA in vitro and may also contribute to a deficient SIgA immunobarrier in COPD.InterpretationLoss of the SIgA immunobarrier in small airways of patients severe COPD is complex and likely results from both pIgR-dependent defects in IgA transcytosis and SIgA degradation.Key MessagesWhat is the key question? Localized SIgA deficiency in small airways is an established driver of COPD pathogenesis, but the mechanism of loss remains unclear. We hypothesized loss of SIgA is due to reduced numbers of pIgR-expressing cells in SIgA-deficient small airways.What is the bottom line? pIgR is primarily expressed by secretory cells in human and murine airways. Although numbers of secretory cells are similar between SIgA-deficient and SIgA-replete airways in COPD, there is reduced expression of pIgR protein, but not mRNA, in SIgA-deficient airways. Additionally, host and bacterial proteases degrade SIgA in vitro, suggesting loss of SIgA may relate to both impaired transcytosis and increased degradation.Why read on? This study highlights the complexity of SIgA immunobarrier maintenance and suggests that strategies aimed at restoring the SIgA immunobarrier will need to account for both impaired transcytosis and degradation by host and/or bacterial proteases.

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“…13 It has been shown that some sIgs of the same isotype are more resistant to proteolytic cleavage than others. For example, Haemophilus influenzae 14 and Neisseria gonorrhoeae, 15 two distinct but common mucosal pathogens, secrete enzymes that can cleave secretory IgA 1 but IgA 2 is resistant to proteolysis by the same enzymes. IgA 2 has a 13-amino-acid deletion that renders this Ig less prone to degradation.…”

Section: Mechanisms Of Immunity At Mucosal Surfacesmentioning

confidence: 99%