Publication: Streptococcus pneumoniae Colonization Disrupts the Microbial Community within the Upper Respiratory Tract of Aging Mice

Colonization of Streptococcus pneumoniae within the upper respiratory tract (URT) of elderly individuals is a major concern, as it often results in the development of pneumonia, which can be deadly in this population. A study published by MIRC Masters’ student Netusha Thevaranjan, under the supervision of Dr. Dawn Bowdish, examined howNetusha-sm aging can change the composition of the respiratory microbial community and consequently, impact bacterial colonization. Using a mouse model of pneumococcal colonization, the study characterized the composition of the URT microbiota in young, middle-aged, and old mice in both the naïve state, and throughout the course of nasopharyngeal colonization with S. pneumoniae. It was shown that the composition of the URT microbiota differs with age, and that colonization with S. pneumoniae in older mice disrupted pre-existing microbial communities.

Furthermore, the study demonstrated that there were several interspecies interactions between S. pneumoniae and resident microbes. In particular,Streptococcus interacted competitively with Staphylococcus and synergistically with Haemophilus. This work provides insight into how aging influences bacterial colonization, and understanding the relationship between these two factors can help create strategies to protect the elderly from age-associated infections and disease. Read More

Publication: A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function

Macrophages play a critical role in innate immunity by detecting, engulfing and destroying pathogenic bacteria and alerting neighbouring immune cells to join the fight against infection. They have many different receptors on their cell surface that allow them to carry out these important processes. A particular group of receptors called Scavenger Receptors are vital to this response. A recent study published in Immunology and Cell Biology by PhD student Kyle Novakowski from the laboratory of Dr. Dawn Bowdish has uncovered a mechanism by which a specific scavenger receptor contributes to macrophage-specific antibacterial immunity.

Scavenger Receptors are evolutionarily ancient and have evolved to recognize a wide array of pathogens by detecting ligands that are common across many pathogenic organisms. A particularly important Scavenger Receptor is Macrophage Receptor with Collagenous Structure, or MARCO. MARCO has been shown to significantly contribute to the clearance of Streptococcus pneumoniae colonization of the nose and in models of pneumococcal pneumonia. The NSERC-funded study took a unique approach to functionally characterizing how MARCO contributes to innate immunity by studying a naturally-occurring variant of the receptor. The study highlighted the importance of a particular domain of the receptor that is required for macrophages to bind and internalize ligands. The study also showed that the domain is necessary to enhance the pro-inflammatory response to pathogenic Streptococcus pneumoniae and can enhance cellular adhesion; both vital to proper macrophage functions.

To read the article, please click here.

Manuscript: The evolution of the scavenger receptor cysteine-rich domain of the class A scavenger receptors

Do you work out? Cause you’re built like a rock! A rock like Dwayne “The Rock” Johnson! You have an impenetrable body thanks to your complex immune system. So how did you get such a sophisticated immune system?

In the Bowdish lab, we do more than just macrophage biology; we also study the evolution of the immune system! The scavenger receptors are a group of receptors that play an important role in your immune system by binding harmful bacteria. Our most recent publication by Yap et al., looks at how these receptors evolved and how evolution has changed their function. These receptors are found in various forms of life such as sharks, frogs, and mammals, but the function and appearance of these receptors has changed over time. Check out the open access….

Extra! Extra! Bowdish Gang Uncovers Truth About IL-17 In The Nose!

The nose is the gateway to the soul… or the lungs at least… making it an important point of first contact between our fragile bodies and the hordes of superbugs attempting to take over the world. Only the brave immunologist has the power to save us from this dire threat. While it’s been known for a few years now that the inflammatory cytokine IL-17A is key to the control of many respiratory infections, no-one has been able to provide any information on the source of this cytokine in nasal infections or how this production is regulated. No more!

Post-doctoral fellow Chris Verschoor and Ph.D. Candidate Mike Dorrington, both trainees in Dr. Dawn Bowdish’s lab have recently had their manuscript “MicroRNA-155 is required for the clearance of Streptococcus pneumoniae from the nasopharynx” accepted for publication in Infection & Immunity. The paper, which was produced in collaboration with Dr. Param Nair of the Firestone Institute, outlines how microRNA- (miR-)155 regulates the immune response to S. pneumoniae colonization in the nasal passages of mice by stimulating the differentiation of Th17 cells. These cells then produce large amounts of IL-17A, which then acts as a chemotactic agent for macrophages, which have awesome swords and stuff that kill the bacteria and save the world! (macrophages are the best cells, by the way)

This paper is the first to show a direct connection between IL-17A-producing T cells and the clearance of a bacterial pathogen from the nasopharynx. It is also the first to show a phenotype of IL-17A deficiency without completely knocking out the cytokine itself. It represents a significant step forward in understanding the regulation of intranasal immune responses to bacterial colonization and how innate and adaptive immune networks collaborate in clearing these events. Way to go Bowdish Lab!

For more information please visit www.bowdish.ca/lab and check out the paper in an upcoming edition of Infection & Immunity.

 

Verschoor CP, Dorrington MG, Novakowski KE, Kaiser J, Radford K, Nair P, Anipindi V, Kaushic C, Surette MG, Bowdish DME. MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx. Infect Immun. 2014 Nov;82(11):4824-33. doi: 10.1128/IAI.02251-14.

Verschoor CP, Dorrington MG, Novakowski KE, Kaiser J, Radford K, Nair P, Anipindi V, Kaushic C, Surette MG, Bowdish DME. MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx. Infect Immun. 2014 Nov;82(11):4824-33. doi: 10.1128/IAI.02251-14.

This paper outlines how microRNA- (miR-)155 regulates the immune response to S. pneumoniae colonization in the nasal passages of mice by stimulating the differentiation of Th17 cells. 

Kaiser JC, Verschoor CP, Surette MG, Bowdish DME. Host cytokine responses distinguish invasive from airway isolates of the Streptococcus milleri/anginosis group. BMC Infect Dis. 2014 Sep 11;14:498. doi: 10.1186/1471-2334-14-498.

Kaiser JC, Verschoor CP, Surette MG, Bowdish DME. Host cytokine responses distinguish invasive from airway isolates of the Streptococcus milleri/anginosis group. BMC Infect Dis. 2014 Sep 11;14:498. doi: 10.1186/1471-2334-14-498.

This paper demonstrates that there are host- and strain- specific responses to isolates of the Streptococcus milleri/anginosis group and that isolates from invasive disease appear to be more immunostimulatory than those from commensal relationships.