Innate immunity of surfactant protein A in experimental otitis media

Abdel-Razek, Osama; Ni, Lan; Yang, Fengyong; Wang, Guirong

doi:10.1177/1753425919866006

Cited by 15 publications

(14 citation statements)

References 40 publications

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“…In the present study, we have found that SP-D is expressed in the mouse ME and ET mucosa, which confirms the previous observation of other studies that found SP-D expressed in porcine ET epithelium [32, 41]. Furthermore, we found that the lack of SP-D could lead to an increase in the inflammatory response to NTHi-induced ME infection and to delay OM resolution as compared to WT mice.…”

Section: Discussionsupporting

confidence: 92%

“…SP-A and SP-D belong to C-type lectins, which function as PRRs and are important in host defense and regulation of inflammation in the lung. Few studies, including our recent SP-A study [32] on the immune response to OM, exist. To the best of our knowledge, no research was carried out for the role of SP-D in OM.…”

Section: Discussionmentioning

confidence: 99%

“…Although the role of SP-D in defense of the tubotympanum remains to be proven, it is likely that a deficiency in these molecules may contribute to the pathogenesis of OM [31]. Recently, we have demonstrated that SP-A contributes to the ME’s innate immunity through enhancing bacterial phagocytosis and killing and modulation of inflammation of the ME mucosa in the OM murine model [32]. In this study, we have used our NTHi-induced OM model and genetically modified SP-D KO mice to examine the role of SP-D and the underlying cellular and molecular mechanisms in the pathogenesis of OM.…”

Section: Introductionmentioning

confidence: 99%

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Role of Surfactant Protein D in Experimental Otitis Media

et al. 2021

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Surfactant protein D (SP-D) is a C-type collectin and plays an important role in innate immunity and homeostasis in the lung. This study studied SP-D role in the nontypeable Haemophilus influenzae (NTHi)-induced otitis media (OM) mouse model. Wild-type C57BL/6 (WT) and SP-D knockout (KO) mice were used in this study. Mice were injected in the middle ear (ME) with 5 μL of NTHi bacterial solution (3.5 × 105 CFU/ear) or with the same volume of sterile saline (control). Mice were sacrificed at 3 time points, days 1, 3, and 7, after treatment. We found SP-D expression in the Eustachian tube (ET) and ME mucosa of WT mice but not in SP-D KO mice. After infection, SP-D KO mice showed more intense inflammatory changes evidenced by the increased mucosal thickness and inflammatory cell infiltration in the ME and ET compared to WT mice (p < 0.05). Increased bacterial colony-forming units and cytokine (IL-6 and IL-1β) levels in the ear washing fluid of infected SP-D KO mice were compared to infected WT mice. Molecular analysis revealed higher levels of NF-κB and NLRP3 activation in infected SP-D KO compared to WT mice (p < 0.05). In vitro studies demonstrated that SP-D significantly induced NTHi bacterial aggregation and enhanced bacterial phagocytosis by macrophages (p < 0.05). Furthermore, human ME epithelial cells showed a dose-dependent increased expression of NLRP3 and SP-D proteins after LPS treatment. We conclude that SP-D plays a critical role in innate immunity and disease resolution through enhancing host defense and regulating inflammatory NF-κB and NLRP3 activation in experimental OM mice.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Surfactant Protein D in Experimental Otitis Media

et al. 2021

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“…However, in terms of the significant changes in protein levels, more significant changes were observed in WT infected compared to KO infected. In an otitis media model of infection with non-typeable Haemophilus influenzae, SP-A was shown to modulate the expression of pro-inflammatory markers, IL-6 and IL-1β, and these peaked at higher levels in SP-A KO mice (17).…”

Section: Bacterial Pathogensmentioning

confidence: 96%

Surfactant Protein-A Function: Knowledge Gained From SP-A Knockout Mice

2022

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Pulmonary surfactant proteins have many roles in surfactant- related functions and innate immunity. One of these proteins is the surfactant protein A (SP-A) that plays a role in both surfactant-related processes and host defense and is the focus in this review. SP-A interacts with the sentinel host defense cell in the alveolus, the alveolar macrophage (AM), to modulate its function and expression profile under various conditions, as well as other alveolar epithelial cells such as the Type II cell. Via these interactions, SP-A has an impact on the alveolar microenvironment. SP-A is also important for surfactant structure and function. Much of what is understood of the function of SP-A and its various roles in lung health has been learned from SP-A knockout (KO) mouse experiments, as reviewed here. A vast majority of this work has been done with infection models that are bacterial, viral, and fungal in nature. Other models have also been used, including those of bleomycin-induced lung injury and ozone-induced oxidative stress either alone or in combination with an infectious agent, bone marrow transplantation, and other. In addition, models investigating the effects of SP-A on surfactant components or surfactant structure have contributed important information. SP-A also appears to play a role in pathways involved in sex differences in response to infection and/or oxidative stress, as well as at baseline conditions. To date, this is the first review to provide a comprehensive report of the functions of SP-A as learned through KO mice.

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“…For example, PRR activation of the NFkB transcription factor cascade by NTHi increased surfactant protein A (SP-A) expression in SP-A knockout mice, causing more severe inflammation. In contrast, wild-type mice showed improved bacterial aggregation, killing and macrophage clearance of the middle ear due to SP-A modulation of the host inflammatory response (Abdel-Razek et al, 2019). Thus, differences in host PRR expression and subsequent signalling pathway activation can lead to differences in how the innate immune response is regulated and how OM disease progresses.…”

Section: Pathogen Recognition and Activation Of Signalling Pathways Within The Innate Immune Responsementioning

confidence: 99%

Innate Immunity in the Middle Ear Mucosa

Massa

Spann

Cripps

2021

Front. Cell. Infect. Microbiol.

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Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

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Innate immunity of surfactant protein A in experimental otitis media

Cited by 15 publications

References 40 publications

Role of Surfactant Protein D in Experimental Otitis Media

Role of Surfactant Protein D in Experimental Otitis Media

Surfactant Protein-A Function: Knowledge Gained From SP-A Knockout Mice

Innate Immunity in the Middle Ear Mucosa

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