Haemophilus influenzae Protein F Mediates Binding to Laminin and Human Pulmonary Epithelial Cells

Jalalvand, Farshid; Su, Yu-Ching; Mörgelin, Matthias; Brant, Marta; Hällgren, Oskar; Westergren‐Thorsson, Gunilla; Singh, Birendra; Riesbeck, Kristian

doi:10.1093/infdis/jis754

Cited by 46 publications

(24 citation statements)

References 43 publications

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“…Potential receptors included those engaged by Tfp expressed by the respiratory tract pathogens Neisseria meningitidis (CD46) (Kallstrom et al, ) and Pseudomonas aeruginosa (asialo‐GM 1 ) (Craig et al, ); host receptors utilized by other known NTHI adhesins (ICAM1, CEACAM1, PAFr); and as a negative control, a protein expressed by endothelial cells (CD105) to which NTHI do not normally either have access to or adhere. Additionally, ECM proteins which NTHI could encounter at the epithelial cell surface and/or are bound by other NTHI outer membrane proteins were assayed including laminin, fibronectin, collagen IV, fibrinogen and vitronectin (Fink et al, ; Hallstrom et al, ; Jalalvand et al, ; Su et al, ). The purified recombinant protein rsPilA (for recombinant soluble PilA), which mimics PilA, the majority subunit of NTHI Tfp (Bakaletz et al, ), served as a surrogate for native pilin protein (Novotny et al, ).…”

Section: Resultsmentioning

confidence: 99%

Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeableHaemophilus influenzae

Novotny

2016

Cellular Microbiology

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Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp-expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp-deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre-incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1, this outcome supported augmented adherence of Tfp-expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp-targeted vaccine for NTHI-induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role.

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Section: Resultsmentioning

confidence: 99%

Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeableHaemophilus influenzae

Novotny

2016

Cellular Microbiology

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“…Spotted fever group Rickettsia species, which are in the Order Rickettsiales with A. phagocytophilum, also use multiple surface proteins to promote entry into host cells (Martinez and Cossart, 2004;Cardwell and Martinez, 2009;Chan et al, 2009;Riley et al, 2010). Moreover, this pathogenic strategy is common among numerous other Gram-negative bacterial pathogens, including Chlamydia pneumoniae (Molleken et al, 2010;, Legionella pneumophila (Garduno et al, 1998;Stone and Abu Kwaik, 1998;Cirillo et al, 2001;Chang et al, 2005;Vandersmissen et al, 2010;Duncan et al, 2011), Bordetella pertussis (Brennan and Shahin, 1996), Haemophilus influenzae (Jurcisek et al, 2007;Giufre et al, 2008;Chang et al, 2011;Dicko et al, 2011;Jalalvand et al, 2013;Singh et al, 2013), and Leptospira species (Barbosa et al, 2006;Pinne et al, 2010;Verma et al, 2010;Zhang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Anaplasma phagocytophilumsurface protein AipA mediates invasion of mammalian host cells

et al. 2014

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Summary Anaplasma phagocytophilum, which causes granulocytic anaplasmosis in humans and animals, is a tick-transmitted obligate intracellular bacterium that mediates its own uptake into neutrophils and non-phagocytic cells. Invasins of obligate intracellular pathogens are attractive targets for protecting against or curing infection because blocking the internalization step prevents survival of these organisms. The complement of A. phagocytophilum invasins is incompletely defined. Here, we report the significance of a novel A. phagocytophilum invasion protein, AipA. A. phagocytophilum induced aipA expression during transmission feeding of infected ticks on mice. The bacterium upregulated aipA transcription when it transitioned from its non-infectious reticulate cell morphotype to its infectious dense-cored morphotype during infection of HL-60 cells. AipA localized to the bacterial surface and was expressed during in vivo infection. Of the AipA regions predicted to be surface-exposed, only residues 1 to 87 (AipA1–87) were found to be essential for host cell invasion. Recombinant AipA1–87 protein bound to and competitively inhibited A. phagocytophilum infection of mammalian cells. Antiserum specific for AipA1–87, but not other AipA regions, antagonized infection. Additional blocking experiments using peptide-specific antisera narrowed down the AipA invasion domain to residues 9 to 21. An antisera combination targeting AipA1–87 together with two other A. phagocytophilum invasins, OmpA and Asp14, nearly abolished infection of host cells. This study identifies AipA as an A. phagocytophilum surface protein that is critical for infection, demarcates its invasion domain, and establishes a rationale for targeting multiple invasins to protect against granulocytic anaplasmosis.

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“…In this situation, a spectrum of extracellular matrix targets is available for recognition by bacterial adhesins. In recent work, fibronectin, laminin, vitronectin, and collagens I and IV have been identified as such targets [7,8,9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 99%

Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for <b><i>Moraxella catarrhalis</i></b>

Abdillahi

Bober²,

Nordin

et al. 2015

J Innate Immun

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Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides potential adhesive targets. Collagen VI is a ubiquitous fibrillar component in the airway mucosa and has been attributed both adhesive and killing properties against Gram-positive bacteria. However, less is known regarding Gram-negative microorganisms. Therefore, in the present study, the interaction of M. catarrhalis with collagen VI was characterized. We found that collagen VI is upregulated in the airways of COPD patients and exposed upon epithelial desquamation. Ex vivo, we inoculated airway biopsies and fibroblasts from COPD patients with M. catarrhalis. The bacteria specifically adhered to collagen VI-containing matrix fibrils. In vitro, purified collagen VI microfibrils bound to bacterial surface structures. The primary adhesion target was mapped to the collagen VI α₂-chain. Upon exposure to collagen VI, bacteria were killed by membrane destabilization in physiological conditions. These previously unknown properties of collagen VI provide novel insights into the extracellular matrix innate immunity by quickly entrapping and killing pathogen intruders.

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Haemophilus influenzae Protein F Mediates Binding to Laminin and Human Pulmonary Epithelial Cells

Abstract: The mucosal pathogen non-typeable Haemophilus influenzae (NTHi) adheres to the respiratory epithelium, or in the case of epithelial damage, to the underlying basement membrane and extracellular matrix that amongst other proteins consists of laminin.

Cited by 46 publications

References 43 publications

Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeableHaemophilus influenzae

Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeableHaemophilus influenzae

Anaplasma phagocytophilumsurface protein AipA mediates invasion of mammalian host cells

Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for <b><i>Moraxella catarrhalis</i></b>

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