Dr Henry Windle
Figure 1 Crystal structure of alkylhydroperoxide reductase (AhpC) from H. pylori. This molecule is essential for H. pylori survival and vaccination with AhpC protects from infection (O’Riordan A. et al., unpublished).
The Infection and Immunity group undertakes research with a pathogen of public health importance: the gastric pathogen Helicobacter pylori. H. pylori infects approximately 50% of the global population and is the causative agent of chronic gastritis and, in some individuals, more serious disease including peptic/duodenal ulceration and gastric cancer.
The aim of our work with H. pylori is to study host-pathogen interactions and to identify mechanisms whereby these interactions lead to either disease progression or protection of the pathogen from the host’s immune response. We are developing vaccines against H. pylori and most recently have identified an efficacious prophylactic vaccine using in vivo models of infection (Fig. 1) and aim to improve on current vaccination strategies by developing antigens tailored to provoke a more potent immune response.
Other areas of current research are related to host-pathogen interactions and include studies on how the bacterium can dampen the innate immune response to H. pylori, and the role of several H. pylori molecules (redox active proteins, metabolic enzymes) in the adaptation of the pathogen to its environment. A typical approach to decipher the physiological function of such proteins is to generate isogenic mutants prior to evaluating the resulting phenotype. Proteomic approaches are also used to study protein-protein interactions between H. pylori molecules both within the bacterium (Fig. 2) and with host cells.
We also have an interest in the relationship between H. pylori infection and the manifestation of nongastric disease states such as iron deficiency anaemia and how this may impact on paediatric growth (Fig. 3). This work is a collaborative project between several European and Latin American partners and is coordinated by TCD and Leeds University (http://www.contentproject.org/).
Key Publications
Childhood Helicobacter pylori
infection and growth impairment in
developing countries: a vicious cycle?
Pediatrics. 119: 754-9, 2007.
Windle, H.J., Kelleher D., Crabtree J.E.
Helicobacter pylori thioredoxin is an
arginase chaperone and guardian
against oxidative and nitrosative
stresses.
Journal of Biological Chemistry 281:
3290 – 3296, 2006.
McGee DJ, Kumar S, Viator RJ, Bolland
JR, Ruiz J, Spadafora D, Testerman TL,
Kelly DJ, Pannell LK, Windle HJ.
Human peripheral and gastric
lymphocyte responses to Helicobacter
pylori NapA and AhpC differ in
infected and uninfected individuals.
Gut, 54: 25 – 32, 2005.
Windle HJ, Ang YS, Morales VA,
McManus R, Kelleher D.
Crystal structure of alkyl
hydroperoxide-reductase (AhpC) from
Helicobacter pylori.
Biochim Biophys Acta. 1753: 240-6,
2005.
Papinutto E, Windle HJ, Cendron L,
Battistutta R, Kelleher D, Zanotti G.,
2005.
Helicobacter pylori activates the early
growth response 1 protein in gastric
epithelial cells.
Infection and Immunity, 72: 3549-60,
2004.
M. M. Abdel-Latif, H. J. Windle, K. A.
Fitzgerald, Y. S. Ang, D. Ni Eidhin,
M. Li-Weber, K. Sabra and D. Kelleher.