Infectious Diseases

Inflammatory cytokines have evolved to disrupt protein biosynthesis in secretory cells prone to viral infection such as mucosal epithelial cells in order to reduce viral replication as a hereto unrecognised element of the immune response

 

On-going Projects

  • Cellular Stress and Viral Infection

    Discovery: Specific cytokines induce Unfolded Protein Response in secretory cells, like goblet cells in the lung, to limit viral replication. Cytokines such as IL-10 and IL-22 suppress this pathway, allowing the virus to replicate uncontrollably inducing increased pathology.

  • Interleukin-22 and Respiratory Syncytial Virus

    Discovery: Endogenous Interleukin-22 unregulated early during respiratory syncytial viral infection. IL-22 by reducing cellular stress, allows virus to propagate uncontrollably, exogenous IL-22 leads to mortality in pre-clinical murine models. Inhibition of IL-22 reduced pathology, reduces mucus secretion and airway hyper-reactivity.

  • Role of the Mucosal Barrier during Infection

    Discovery: Mucosal barrier integrity is a key component of the immune defence against pathogens. Our work is trying to understand how to promote barrier integrity during infection.

Publications

A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria

Nhu NTK, Rahman MA, Goh KGK, Kim SJ, Phan MD, Peters KM, Alvarez-Fraga L, Hancock SJ, Ravi C, Kidd TJ, Sullivan MJ, Irvine KM, Beatson SA, Sweet MJ, Irwin AD, Vukovic J, Ulett GC, Hasnain SZ, Schembri MA. Nat Commun. 2024 Feb 21;15(1):1441.

Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective.

Sinha R, Ngo MD, Bartlett S, Bielefeldt-Ohmann H, Keshvari S, Hasnain SZ, Donovan ML, Kling JC, Blumenthal A, Chen C, Short KR, Ronacher K. Front. Cell Infect Microbiol. Jul 2021.

DP1 prostanoid receptor activation increases the severity of an acute lower respiratory viral infection in mice via TNF-α-induced immunopathology.

Ullah MA, Rittchen S, Li J, Hasnain SZ, Phipps S. Mucosal Immunol. 2021 Jul;14(4):963-972. Epub 2021 Apr 20.

Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion.

Hasnain SZ, Dawson PA, Lourie R, Hutson P, Tong H, Grencis RK, McGuckin MA, Thornton DJ. PLoS Pathog. (2017) 13;13(2):e1006218.

Mucin  gene  deficiency  in  mice  impairs host resistance to an enteric parasitic infection.

Hasnain  SZ, Wang  H, Ghia JE, Haq  N, Deng  Y, Velcich  A, Grencis  RK, Thornton  DJ and  Khan  W I.   Gastroenterology.  (2010) 138(5):763-71.

Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells

Moniruzzaman M, Rahman MA, Wang R, Wong KY, Chen AC, Mueller A, Taylor S, Harding A, Illankoon T, Wiid P, Sajiir H, Schreiber V, Burr LD, McGuckin MA, Phipps S, Hasnain SZ. J Exp Med. 2023 Nov 6;220(11):e20230106.

Influence of the MUC1 Cell Surface Mucin on Gastric Mucosal Gene Expression Profiles in Response to Helicobacter pylori Infection in Mice.

Sheng YH, Ng GZ, Summers KM, Every AL, Price G, Hasnain SZ, Sutton P, McGuckin MA. Front Cell Infect Microbiol. 2020 Jul 24;10:343. doi: 10.3389/fcimb.2020.00343

High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier.

Hulme KD, Yan L, Marshall RJ, Bloxham CJ, Upton KR, Hasnain SZ, Bielefeldt-Ohmann H, Loh Z, Ronacher K, Chew KY, Gallo LA, Short KR. eLife (2020); 9:e56907.DOI: 10.7554/eLife.56907

Serine Protease(s) secreted by the nematode Trichuris muris degrade the mucus barrier. 

Hasnain SZ, McGuckin	MA, Grencis RK	and Thornton DJ. PLoS Neglected Tropical Diseases. (2012) 6(10):e1856

Changes in the mucosal barrier during acute and chronic Trichuris muris infection.

Hasnain SZ, Thornton DJ and Grencis RK. Parasite Immunology. (2011) 33(1): 44-45.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier

McGuckin MA, Davies JM, Felgner P, Wong KY, Giri R, He Y, Moniruzzaman M, Kryza T, Sajiir H, Hooper JD, Florin TH, Begun J, Oussalah A, Hasnain SZ, Hensel M, Sheng YH. Cell Mol Gastroenterol Hepatol. 2023;16(6):985-1009.

PPARγ is reduced in the airways of non-CF bronchiectasis subjects and is inversely correlated with the presence of Pseudomonas aeruginosa.

Burr LD, Rogers GB, Chen AC, Taylor SL, Bowler SD, Keating RL, Martin ML, Hasnain SZ, McGuckin MA. PLoS One. 2018 Aug 16;13(8):e0202296. doi:10.1371/journal.pone.0202296.

Immune regulation of the unfolded protein response at the mucosal barrier in viral infection.

Wang R, Moniruzzaman M, Shuffle E, Lourie R,  Hasnain SZ. Clin Transl Immunology. 2018. 3;7(4):e1014. doi:10.1002/cti2.1014. eCollection 2018. Review.

Muc5ac: a critical  component mediating   the   rejection    of   the   enteric  nematodes.

Hasnain SZ, Evans  C,  Roy  M,  Gallagher  AL, Kindrachuk  KN,  Barron  L, Dickey  BF, Wilson MS, Wynn TA, Grencis RK and Thornton DJ. Journal  of  Experimental Medicine. (2011) 208 (5): 893.

A new role for mucins in immunity: insights from gastrointestinal nematode infection.

Hasnain SZ, Gallagher A, Grencis RK and Thornton DJ. The International Journal of Biochemistry & Cell Biology. (2012). S1357-2725(12)00357-3.