Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen of the human respiratory tract responsible for mucosal diseases in the upper and lower airways. To date, there is no vaccine or treatment available against this pathogen. NTHi utilizes a variety of proteins to adhere to and colonize the surface of epithelial cells, which is crucial for its invasion.
The C-Type Lectin receptor (CRL) is known as the major β-glucan receptor expressed in myeloid cells and is responsible for targeting respiratory fungal pathogens. Recent studies have shown that CRL can recognize NTHi and enhance the proinflammatory response against this pathogen in human airway epithelial cells. However, the specific ligand of NTHi responsible for this interaction remains unknown.
In this project, our aim is to identify the molecule responsible for the interaction between NTHi and CRL, with the goal of finding a promising target for vaccine development to treat NTHi infections. We have obtained some preliminary data that suggest a group of NTHi surface proteins are capable of binding to CRL. This finding suggests that this receptor may have the ability to detect ligands from a broader spectrum of pathogens, not limited to fungal origins.
Currently, our focus is to determine whether the interaction between NTHi surface proteins and CRL can trigger an immune response, as this information will be valuable in identifying potential vaccine candidates.
Start date is flexible.
Contact: Prof. Kristian Riesbeck, Dept of Translational Medicine, http://research.med.lu.se/kristian-riesbeck
Suggested reading:
- Su YC, Mattsson E, Singh B, Jalalvand F, Murphy TF, Riesbeck K. The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization. J Infect Dis. 2019;220(6):1049-1060.
- Heyl KA, Klassert TE, Heinrich A, Müller MM, Klaile E, Dienemann H, Grünewald C, Bals R, Singer BB, Slevogt H. Dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable Haemophilus influenzae. mBio. 2014;5(5)
- Thofte O, Su YC, Brant M, et al. EF-Tu From Non-typeable Haemophilus influenzae Is an Immunogenic Surface-Exposed Protein Targeted by Bactericidal Antibodies. Front Immunol. 2018;9:2910.