Nasal Delivery of a Commensal Pasteurellaceae Species Inhibits Nontypeable Haemophilus influenzae Colonization and Delays Onset of Otitis Media in Mice
| Autor: | Sharon L. Clark, Peter Richmond, Camilla de Gier, Katrien M. J. Sutherland, Lea-Ann S. Kirkham, Janessa Pickering, Ruth B. Thornton, Caitlyn Granland, Naomi M. Scott, Jean-Francois Lauzon-Joset, Jeroen D. Langereis, Deborah H. Strickland |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Haemophilus Infections 030106 microbiology Immunology lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Colony Count Microbial medicine.disease_cause Microbiology Haemophilus influenzae 03 medical and health sciences Nasopharynx microbial interference Antibiosis otorhinolaryngologic diseases medicine Influenza A virus Animals Colonization Administration Intranasal bacterial therapy Mice Inbred BALB C biology Influenza A Virus H3N2 Subtype Pasteurellaceae otitis media Bacterial Infections biology.organism_classification medicine.disease 3. Good health Disease Models Animal Nasal Mucosa 030104 developmental biology Infectious Diseases Otitis Haemophilus haemolyticus Carrier State Coinfection Cytokines Muribacter muris Parasitology Nasal administration medicine.symptom |
| Zdroj: | Infection and Immunity, 88 Infection and Immunity Infection and Immunity, 88, 4 |
| ISSN: | 0019-9567 |
| Popis: | Nasopharyngeal colonization with nontypeable Haemophilus influenzae (NTHi) is a prerequisite for developing NTHi-associated infections, including otitis media. Therapies that block NTHi colonization may prevent disease development. We previously demonstrated that Haemophilus haemolyticus, a closely related human commensal, can inhibit NTHi colonization and infection of human respiratory epithelium in vitro. We have now assessed whether Muribacter muris (a rodent commensal from the same family) can prevent NTHi colonization and disease in vivo using a murine NTHi otitis media model. Nasopharyngeal colonization with nontypeable Haemophilus influenzae (NTHi) is a prerequisite for developing NTHi-associated infections, including otitis media. Therapies that block NTHi colonization may prevent disease development. We previously demonstrated that Haemophilus haemolyticus, a closely related human commensal, can inhibit NTHi colonization and infection of human respiratory epithelium in vitro. We have now assessed whether Muribacter muris (a rodent commensal from the same family) can prevent NTHi colonization and disease in vivo using a murine NTHi otitis media model. Otitis media was modeled in BALB/c mice using coinfection with 1 × 104.5 PFU of influenza A virus MEM H3N2, followed by intranasal challenge with 5 × 107 CFU of NTHi R2866 Specr. Mice were pretreated or not with an intranasal inoculation of 5 × 107 CFU M. muris 24 h before coinfection. NTHi and M. muris viable counts and inflammatory mediators (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, keratinocyte chemoattractant [KC], and IL-10) were measured in nasal washes and middle ear tissue homogenate. M. muris pretreatment decreased the median colonization density of NTHi from 6 × 105 CFU/ml to 9 × 103 CFU/ml (P = 0.0004). Only 1/12 M. muris-pretreated mice developed otitis media on day 5 compared to 8/15 mice with no pretreatment (8% versus 53%, P = 0.0192). Inflammation, clinical score, and weight loss were also lower in M. muris-pretreated mice. We have demonstrated that a single dose of a closely related commensal can delay onset of NTHi otitis media in vivo. Human challenge studies investigating prevention of NTHi colonization are warranted to reduce the global burden of otitis media and other NTHi diseases. |
| Databáze: | OpenAIRE |
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