The Clark lab investigates bacterial-driven immune modulation in the respiratory tract. The upper respiratory tract is home to a diverse microbial community that includes both commensal and opportunistic bacterial pathogens. Research in the lab explores how exposure to these bacteria influences upper and lower respiratory tract inflammation and disease, with a focus on the innate immune response to acute infection.
One project area investigates bacterial activation of pathways leading to the secretion of IL-10, the prototypical anti-inflammatory cytokine, and how this response influences inflammation and susceptibility to secondary infections. Another project area investigates how commensal airway bacteria activate immune responses which contribute to protection against bacterial pathogens. We model host-pathogen interactions using Streptococcus pneumoniae, the most common cause of acute otitis media and bacterial pneumonia in children, Haemophilus influenzae, and commensal bacterial species. The long-term goal of this work is to identify new therapeutic approaches for the clinically significant problems of respiratory tract infection and inflammation.
Publications
Horn, K.J., Schopper, M.A., Drigot, Z.G., Clark, S.E. Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung. Nat Commun 13, 3321 (2022). doi: 10.1038/s41467-022-31074-0
Horn KJ, Jaberi Vivar AC, Arenas V, Andani S, Janoff EN and Clark SE. Corynebacterium species inhibit Streptococcus pneumoniae colonization and infection of the mouse airway. Front. Microbiol. 2022 Jan;12:804935. doi: 10.3389/fmicb.2021.804935
Horn KJ, Schopper MA, Drigot ZG, Clark SE. Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung. Nat Commun. 2022 Jun 9;13(1):3321. PubMed PMID: 35680890
Horn KJ, Jaberi Vivar AC, Arenas V, Andani S, Janoff EN, Clark SE. Corynebacterium Species Inhibit Streptococcus pneumoniae Colonization and Infection of the Mouse Airway. Front Microbiol. 2021;12:804935. PubMed PMID: 35082772
Clark SE, Schmidt RL, Aguilera ER, Lenz LL. IL-10-producing NK cells exacerbate sublethal Streptococcus pneumoniae infection in the lung. Transl Res. 2020 Dec;226:70-82. PubMed PMID: 32634590
Clark SE. Commensal bacteria in the upper respiratory tract regulate susceptibility to infection. Curr Opin Immunol. 2020 May 13;66:42-49. [Epub ahead of print] PubMed PMID: 32416468
Clark SE, Schmidt RL, McDermott DS, Lenz LL. A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection. Cell Rep. 2018 May 29;23(9):2582-2594. PubMed PMID: 29847790
Soderborg TK, Clark SE, Mulligan CE, Janssen RC, Babcock L, Ir D, Young B, Krebs N, Lemas DJ, Johnson LK, Weir T, Lenz LL, Frank DN, Hernandez TL, Kuhn KA, D'Alessandro A, Barbour LA, El Kasmi KC, Friedman JE. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018 Oct 26;9(1):4462. PubMed PMID: 30367045
Clark SE, Filak HC, Guthrie BS, Schmidt RL, Jamieson A, Merkel P, Knight V, Cole CM, Raulet DH, Lenz LL. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection. PLoS Pathog. 2016 Jun;12(6):e1005708. PubMed PMID: 27295349
Clark SE, Eichelberger KR, Weiser JN. Evasion of killing by human antibody and complement through multiple variations in the surface oligosaccharide of Haemophilus influenzae. Mol Microbiol. 2013 May;88(3):603-18. PubMed PMID: 23577840
Clark SE, Weiser JN. Microbial modulation of host immunity with the small molecule phosphorylcholine. Infect Immun. 2013 Feb;81(2):392-401. PubMed PMID: 23230294
Clark SE, Snow J, Li J, Zola TA, Weiser JN. Phosphorylcholine allows for evasion of bactericidal antibody by Haemophilus influenzae. PLoS Pathog. 2012;8(3):e1002521. PubMed PMID: 22396641
Nakamura S, Shchepetov M, Dalia AB, Clark SE, Murphy TF, Sethi S, Gilsdorf JR, Smith AL, Weiser JN. Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae. PLoS Pathog. 2011 Jan 6;7(1):e1001247. PubMed PMID: 21253576
Clark SE, Jude BA, Danner GR, Fekete FA. Identification of a multidrug efflux pump in Flavobacterium johnsoniae. Vet Res. 2009 Nov-Dec;40(6):55. PubMed PMID: 19558960
McIntosh D, Cunningham M, Ji B, Fekete FA, Parry EM, Clark SE, Zalinger ZB, Gilg IC, Danner GR, Johnson KA, Beattie M, Ritchie R. Transferable, multiple antibiotic and mercury resistance in Atlantic Canadian isolates of Aeromonas salmonicida subsp. salmonicida is associated with carriage of an IncA/C plasmid similar to the Salmonella enterica plasmid pSN254. J Antimicrob Chemother. 2008 Jun;61(6):1221-8. PubMed PMID: 18375380
Horn KJ, Vivar ACJ, Arenas V, Andani S, Janoff EN, Clark SE. Corynebacterium species inhibit Streptococcus pneumoniae colonization and infection of the mouse airway. Frontiers in Microbiology. Forthcoming 2021.