Background: Recommendations regarding head and neck paragangliomas (HNPGL) have undergone a fundamental reorientation in the last decade as a result of increased understanding of the genetic and pathophysiologic basis of these disorders. Objective: We aim to provide an overview of HNPGL and recent discoveries regarding their molecular genetics, along with updated recommendations on workup, treatment, and surveillance, and their implications for otolaryngologists treating patients with these disorders. Results: SDHx susceptibility gene mutations, encoding subunits of the enzyme succinate dehydrogenase (SDH), give rise to the Hereditary Pheochromocytoma/Paraganglioma Syndromes. SDHA, SDHB, SDHC, SDHD, and SDHAF2 mutations each result in unique phenotypes with distinct penetrance and risk for variable tumor development as well as metastasis. Genetic and biochemical testing is recommended for every patient with HNPGL. Multifocal disease should be managed in multi-disciplinary fashion. Patients with SDHx mutations require frequent biochemical screening and whole-body imaging, as well as lifelong follow-up with an expert in hereditary pheochromocytoma and paraganglioma syndromes. Conclusion: Otolaryngologists are likely to encounter patients with HNPGL. Keeping abreast of the latest recommendations, especially regarding genetic testing, workup for additional tumors, multi-disciplinary approach to care, and need for lifelong surveillance, will help otolaryngologists appropriately care for these patients.

This study investigates how specific members of the lung microbiome influence the early immune response to infection. Prevotella species are a major component of the endogenous airway microbiota. Increased abundance of Prevotella melaninogenica correlates with reduced infection with the bacterial pathogen Streptococcus pneumoniae, indicating a potentially beneficial role. Here, we show that P. melaninogenica enhances protection against S. pneumoniae, resulting in rapid pathogen clearance from the lung and improved survival in a mouse lung co-infection model. This response requires recognition of P. melaninogenica lipoproteins by toll-like receptor (TLR)2, the induction of TNFα, and neutrophils, as the loss of any of these factors abrogates Prevotella-induced protection. Improved clearance of S. pneumoniae is associated with increased serine protease-mediated killing by lung neutrophils and restraint of P. melaninogenica-induced inflammation by IL-10 in co-infected mice. Together, these findings highlight innate immune priming by airway Prevotella as an important protective feature in the respiratory tract.

4. Laryngoscope, 128:2261-2267, 2018.

No abstract

Commensal (non-pathogenic) bacteria play an important role in protecting against disease. In both humans and animal models, the depletion of commensal bacteria by antibiotics increases susceptibility to pathogen infection of the lung. However, the specific commensal bacteria which contribute to this protective effect remain undefined. In the respiratory tract, Prevotella species are frequently associated with health rather than disease, indicating a potentially beneficial role. Specifically, some Prevotella species negatively correlate with infection with the bacterial pathogen Streptococcus pneumoniae, the most common cause of bacterial pneumonia. We recapitulated this relationship in mice, where we find that exposure to an airway commensal Prevotella species improves rapid clearance of S. pneumoniae from the lung. The use of heat-killed Prevotella was sufficient for inducing protection against S. pneumoniae, which was lost in mice depleted of the pro-inflammatory cytokine TNF-α. These results suggest that Prevotella exposure primes an immune response that increases protection against S. pneumoniae infection in the lung. We further find that mouse neutrophils both secrete TNF-α and are improved in their ability to kill S. pneumoniae following Prevotella exposure. Together, these findings indicate that airway Prevotella species can enhance protection against S. pneumoniae lung infection by activating an innate immune response that increases bacterial clearance.