Pili play an important role in enhancing the bacterial clearance from the middle ear in a mouse model of acute otitis media with<i>Moraxella catarrhalis</i>

Kawano, Toshiaki; Hirano, Takashi; Kodama, Satoru; Mitsui, Marcelo Takahiro; Ahmed, Kamruddin; Nishizono, Akira; Suzuki, Masashi

doi:10.1111/2049-632x.12025

Cited by 7 publications

(3 citation statements)

References 49 publications

(68 reference statements)

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“…In experimental endophthalmitis, the pili-deficient B. cereus burden was lower than that of the pili-containing B. cereus burden, suggesting that the latter strain was better controlled by the intraocular immune response. Conversely, Moraxella- containing pili were cleared from a mouse otitis media model more readily than pili-deficient strains (Kawano et al, 2013). It has also been suggested that pili-deficient bacteria escape phagocytosis because they are less adherent.…”

Section: Discussionmentioning

confidence: 99%

The role of pili in Bacillus cereus intraocular infection

Callegan

Parkunan

Randall

et al. 2017

Experimental Eye Research

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Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p>0.05, every 2 h, 0-18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p≤0.05, 3-12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity of the inflammatory response, these results suggest a potential role for pili in protecting B. cereus from clearance during the early stages of endophthalmitis, which is a newly described virulence mechanism for this organism and this infection.

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Section: Discussionmentioning

confidence: 99%

The role of pili in Bacillus cereus intraocular infection

Callegan

Parkunan

Randall

et al. 2017

Experimental Eye Research

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“…TLR 2, 4, 5, and 9 mRNA expression is up-regulated in neutrophils infected with M. catarrhalis with and without pili. 97 When TLR4 is non-functional in C3H/HeJ mice, NTHi infections are prolonged and phagocytosis as well as phagosome maturation in PMNs are impaired. 98 Thus, TLR4 appears to be intimately involved in the bactericidal function of PMNs and plays a vital role in eradicating NTHi infection in the middle ear.…”

Section: Neutrophilsmentioning

confidence: 99%

Role of innate immunity in the pathogenesis of otitis media

Mittal

Kodiyan

Gerring

et al. 2014

International Journal of Infectious Diseases

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Summary Otitis media (OM) is a public health problem in both developed and developing countries. It is the leading cause of hearing loss and represents a significant healthcare burden. In some cases, acute OM progresses to chronic suppurative OM (CSOM), characterized by effusion and discharge, despite antimicrobial therapy. The emergence of antibiotic resistance and potential ototoxicity of antibiotics has created an urgent need to design non-conventional therapeutic strategies against OM based on modern insights into its pathophysiology. In this article, we review the role of innate immunity as it pertains to OM and discuss recent advances in understanding the role of innate immune cells in protecting the middle ear. We also discuss the mechanisms utilized by pathogens to subvert innate immunity and thereby overcome defensive responses. A better knowledge about bacterial virulence and host resistance promises to reveal novel targets to design effective treatment strategies against OM. The identification and characterization of small natural compounds that can boost innate immunity may provide new avenues for the treatment of OM. There is also a need to design novel methods for targeted delivery of these compounds into the middle ear, allowing higher therapeutic doses and minimizing systemic side effects.

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“…Studies in animal models have demonstrated the crucial role of TLRs and TLR-dependent signaling cascades in the resolution of OM [44, 46, 70]. TLR mutations caused prolongation of OM in mice, while both TLR2- and TLR4-deficient mice exhibit persistent inflammation with impaired bacterial clearance and delays in OM recovery.…”

Section: The Tlr Familymentioning

confidence: 99%

Innate Immunity: Orchestrating Inflammation and Resolution of Otitis Media

Kurabi

Pak

Ryan

et al. 2016

Curr Allergy Asthma Rep

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Otitis media (OM) is a common disease in young children, accounting for more office visits and surgeries than any other pediatric condition. It is associated with an estimated cost of five billion dollars annually in the USA. Moreover, chronic and recurrent middle ear (ME) disease leads to hearing loss during critical periods of language acquisition and learning leading to delays in reaching developmental milestones and risking permanent damage to the ME and inner ear in severe cases. Therefore, research to understand the disease pathogenesis and identify new therapeutics is important. Although OM is a multifactorial disease, targeting the molecular mechanisms that drive inflammation and OM resolution is critical. In this review, we discuss the current evidence suggesting that innate immune receptors and effectors play key roles in OM by mediating both the ME inflammatory responses and recovery.

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Pili play an important role in enhancing the bacterial clearance from the middle ear in a mouse model of acute otitis media withMoraxella catarrhalis

Cited by 7 publications

References 49 publications

The role of pili in Bacillus cereus intraocular infection

The role of pili in Bacillus cereus intraocular infection

Role of innate immunity in the pathogenesis of otitis media

Innate Immunity: Orchestrating Inflammation and Resolution of Otitis Media

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