The frailty and susceptibility of the elderly population is often accepted as a sad but inevitable fact. The processes and mechanisms underlying this phenomenon is, however, relatively unexplored and currently unknown. A new study by Dr. Chis Verschoor and colleagues establish a potential role for TNFα in compromising immune functions by affecting neutrophil maturation.
The study, published in Molecular Immunology, reveals an increased frequency of circulating neutrophils in advanced-age frail elderly individuals compared to young or community-dwelling elderly individuals. The neutrophils isolated from advanced-age frail elderly individuals are furthermore immature, with increased expression of the maturation markers cd11b and HLA-DR. The frequency of cd11b positive neutrophils was associated with higher plasma concentration of TNFα, and using experimental models, the authors demonstrate a critical role for TNFα in neutrophil expression of cd11b. The studies provide important clues to the mechanisms underlying increased susceptibility and frailty of advanced-aged individuals.
Dr. Verschoor has been working with Associate Professor Dawn Bowdish for his research fellowship and has published 14 papers in the past year, including five first author publications. By adopting innovative research strategies to address pressing scientific issues, Dr. Verschoor has elevated the research on immune functions in the frail elderly considerably. The dedicated Dr. Verschoor is a critical member of the Bowdish lab, and highly appreciated at MIRC. Dr. Verschoor has trained a number of students at MIRC, and helped them achieve scientific excellence.
Sick of getting older? Associate Professor Dawn Bowdish might not be able to slow down the passing of time, but her research is advancing our understanding of immune aging, knowledge that can be used to prevent and better treat illness among the elderly. Dr. Bowdish’s research is now featured in a video produced by Research2Reality. This ground-breaking initiative brings attention to innovative and leading edge research in Canada, and the world-class scientists engaged in it. The video series is continually updated to share the impact of recent discoveries, and to celebrate the success of researchers that establish the new frontiers of science.
Dr. Bowdish is determined to understand increased susceptibility to infection in the elderly, and has built a strong case for an involvement of age related changes to immunity. The research is largely focused on the role of macrophages in host defenses against pathogens, but as any successful researcher, Dr. Bowdish casts a wide net. The research is additionally aimed at developing novel immunomodulatory therapies to treat infectious disease, and prevent early demise in a frail population.
Watch the video on the Research2Reality website.
Dr. Charu Kaushic - has been awarded a CIHR Mucosal Team Grant to study whether alterations to female sex hormones and vaginal microbiota affect the inflammatory processes responsible for increased HIV susceptibility. Female sex hormones, such as estrogen and progesterone, are known to have a role in determining the susceptibility of the vaginal tract to HIV infection. These hormones also maintain reproductive health by controlling the local colonization of beneficial microbiota. An altered microbiota may lead to inflammation, which increases the risk of HIV infection.
The CIHR Mucosal Team, which includes Drs. Kaushic, Ashkar and Bowdish from MIRC and other Faculty of Health Science researchers including Drs. Mike Surette, Fiona Smaill and Paul Forsythe will try two innovative hormone-based approaches for HIV prevention. The first approach will utilize a combination of clinical studies and experimental models to determine whether progesterone based contraceptives enhance inflammation by disrupting the beneficial flora of microorganisms. The second approach will explore whether delivering small amounts of probiotics, or estrogen, can help in colonization by healthy vaginal microbiota and reduce the risk of contracting HIV. Unlike most existing HIV prevention techniques that utilize anti-retroviral approaches, these approaches are more natural and based on improving reproductive health.
A paper by Drs. Martin Stampfli and Abraham Roos is featured in an editorial piece, as well as on the cover of the latest issue of the American Journal of Respiratory and Critical Care Medicine (AJRCCM). The paper by Roos et al. demonstrates increased expression of IL-17A in advanced chronic obstructive pulmonary disease (COPD), and furthermore provides evidence of a functional role for IL-17A in cigarette smoke-induced lymphoid follicle neogenesis. IL-17A plays a multifaceted role in COPD, and has previously been linked to airway neutrophilia and host defenses in experimental models relevant to COPD. Drs. Bozinovski and Vlahos, the authors of the editorial, point out that IL-17A represents a molecular marker associated with the persistence of cigarette smoke-induced inflammation following smoking cessation. Targeting IL-17A may thus be beneficial to reduce chronic and persistent inflammation, without compromising lung host defenses. The authors of the editorial note that distinct cellular subsets expressing IL-17A may play different roles in airway inflammation and host defenses. Additional studies further defining and investigating the cellular sources of IL-17A in end-stage COPD are thus warranted to determine the contribution of different IL-17A+ subsets in the disease. In light of this, the localization of IL-17A to mast cells, demonstrated by Roos et al., is a finding of particular importance to the field.
Read the editorial in the June issue of AJRCCM.
MIRC's newest faculty member is already making headlines. Assistant professor Matthew Miller is featured in this weeks FHS newsletter, in response to his latest research findings and interviews in The Hamilton Spectator, CBC Hamilton and CHML radio.
Read the full news article below.
One punch to knock out flu
The fact that this year’s flu shot is not a good match against this year’s influenza strain is well known, and has happened before. But now researchers at MIRC and the Icahn School of Medicine at Mount Sinai, New York say that a universal flu vaccine may be on the horizon, thanks to the recent discovery of a new class of antibodies that are capable of neutralizing a wide range of influenza A viruses.
“Unlike seasonal vaccines, which must be given annually, this type of vaccine would only be given once, and would have the ability to protect against all strains of flu, even when the virus mutates,” said Matthew Miller, an assistant professor in McMaster’s Department of Biochemistry and Biomedical Sciences at the Michael G. DeGroote School of Medicine. “This would prevent the occurrence of flu pandemics and poor vaccine efficiency in the case of mismatches, which actually occurred this year.”
In the study, published today in the Journal of Virology, senior author Miller and his colleagues show that when comparing the potency of an isolated strain-specific flu antibody (the type that current vaccines generate) with an isolated broadly-neutralizing flu antibody (the type generated by universal vaccines) in a lab setting, the latter have much weaker neutralization activity than the strain-specific antibodies.
Professor Brian Lichty of MIRC has teamed up with long-term collaborators Dr. John Bell (the Ottawa Hospital and the University of Ottawa), and Dr. David Stojdl (the Children's Hospital of Eastern Ontario and the University of Ottawa) to create Turnstone Biologics Inc. The startup biotech company will focus on developing new cancer therapies that harness the immune system, including a oncolytic virus- and vaccine-based treatment. The investigators have already demonstated unprecedented tumor fighting capabilities of the Maraba virus in experimental models, and expect to translate their findings into improved outcomes for cancer patients. The therapy represents the first tumor-targeted oncolytic vaccine that includes a sustained anti-cancer immune response. The founding partners’ goal to accelerate commercialization and clinical translation of immune-based cancer treatments is funded by both academic and public institutions, as well as charitable foundations. Read more about Dr. Lichty and Turnstone Biologics at the McMaster Faculty of Health Science and the Hamilton Spectator.
IL-4 has long been known to be a driver of intestinal Th2 priming in food allergy, however the source and control of this cytokine during initiation of type 2 immunity remains unclear. This month, work done by the research group of Professor Manel Jordana at MIRC in collaboration with members of the Farncombe Family Digestive Health Research Institute and the Department of Respiratory Inflammation and Autoimmunity at Medimmune was published in Mucosal Immunology. The paper by Chu et al. narrows down the key players in initiation and regulation of the allergic Th2 response. The researchers show that IL-4 required for oral sensitization to peanuts is CD4+ T cell-intrinsic, driven by OX40L co-stimulation. The autocrine/paracrine IL-4 signaling leads to stabilization of the Th2 state and is independent of innate lymphocytes including ILCs, as well as NKT and γδ T cells. We look forward to future work from the Jordana lab helping to solve the puzzle of oral sensitization and food allergy!
By Dessi Loukov