» Articles » PMID: 28968876

Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus Influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease

Overview
Journal J Infect Dis
Date 2017 Oct 3
PMID 28968876
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Nontypeable Haemophilus influenzae (NTHi) persists in the airways in chronic obstructive pulmonary disease (COPD). NTHi expresses 4 immunoglobulin (Ig)A protease variants (A1, A2, B1, B2) with distinct cleavage specificities for human IgA1. Little is known about the different roles of IgA protease variants in NTHi infection.

Methods: Twenty-six NTHi isolates from a 20-year longitudinal study of COPD were analyzed for IgA protease expression, survival in human respiratory epithelial cells, and cleavage of lysosomal-associated membrane protein 1 (LAMP1).

Results: IgA protease B1 and B2-expressing strains showed greater intracellular survival in host epithelial cells than strains expressing no IgA protease (P < .001) or IgA protease A1 or A2 (P < .001). Strains that lost IgA protease expression showed reduced survival in host cells compared with the same strain that expressed IgA protease B1 (P = .006) or B2 (P = .015). IgA proteases B1 and B2 cleave LAMP1. Passage of strains through host cells selected for expression of IgA proteases B1 and B2 but not A1.

Conclusions: IgA proteases B1 and B2 cleave LAMP1 and mediate intracellular survival in respiratory epithelial cells. Intracellular persistence of NTHi selects for expression of IgA proteases B1 and B2. The variants of NTHi IgA proteases play distinct roles in pathogenesis of infection.

Citing Articles

Persistent microbial infections and idiopathic pulmonary fibrosis - an insight into pathogenesis.

Shadid A, Rich H, DeVaughn H, Domozhirov A, Doursout M, Weng-Mills T Front Cell Infect Microbiol. 2025; 14:1479801.

PMID: 39760094 PMC: 11695292. DOI: 10.3389/fcimb.2024.1479801.


Substitutions in the nonactive site of the passenger domain on the activity of immunoglobulin A1 protease.

Chen C, Ho C Infect Immun. 2024; 92(8):e0019324.

PMID: 38990045 PMC: 11320935. DOI: 10.1128/iai.00193-24.


Epidemic Trends and Biofilm Formation Mechanisms of Haemophilus influenzae: Insights into Clinical Implications and Prevention Strategies.

Xiao J, Su L, Huang S, Liu L, Ali K, Chen Z Infect Drug Resist. 2023; 16:5359-5373.

PMID: 37605758 PMC: 10440118. DOI: 10.2147/IDR.S424468.


Secretory Immunoglobulin A Immunity in Chronic Obstructive Respiratory Diseases.

De Fays C, Carlier F, Gohy S, Pilette C Cells. 2022; 11(8).

PMID: 35456002 PMC: 9027823. DOI: 10.3390/cells11081324.


MAIT Cell Activation and Functions.

Hinks T, Zhang X Front Immunol. 2020; 11:1014.

PMID: 32536923 PMC: 7267072. DOI: 10.3389/fimmu.2020.01014.


References
1.
Murphy T, Brauer A, Schiffmacher A, Sethi S . Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004; 170(3):266-72. DOI: 10.1164/rccm.200403-354OC. View

2.
Fernaays M, Lesse A, Cai X, Murphy T . Characterization of igaB, a second immunoglobulin A1 protease gene in nontypeable Haemophilus influenzae. Infect Immun. 2006; 74(10):5860-70. PMC: 1594874. DOI: 10.1128/IAI.00796-06. View

3.
Hotomi M, Arai J, Billal D, Takei S, Ikeda Y, Ogami M . Nontypeable Haemophilus influenzae isolated from intractable acute otitis media internalized into cultured human epithelial cells. Auris Nasus Larynx. 2009; 37(2):137-44. DOI: 10.1016/j.anl.2009.03.012. View

4.
Reinholdt J, Kilian M . Comparative analysis of immunoglobulin A1 protease activity among bacteria representing different genera, species, and strains. Infect Immun. 1997; 65(11):4452-9. PMC: 175640. DOI: 10.1128/iai.65.11.4452-4459.1997. View

5.
Sethi S, Murphy T . Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008; 359(22):2355-65. DOI: 10.1056/NEJMra0800353. View