Surfactant proteins and innate immunity of otitis media

Abstract

Otitis media (OM) is the most common disease among young children and one of the most frequent reasons to visit the pediatrician. Development of OM requires nasopharyngeal colonization by a pathogen which must gain access to the tympanic cavity through the eustachian tube (ET) along with being able to overcome the defense mechanisms of the immune system and middle ear mucosa. OM can be caused by viral or bacterial infection. The three main bacterial pathogens are Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis. Innate immunity is important in OM resolution as the disease occurs in very young children before the development of specific immunity. Elements of innate immunity include natural barriers and pattern recognition receptors such as Toll like receptors (TLRs), and Nod like receptors (NLRs). Surfactant proteins A (SP-A) and D (SP-D) act as pattern recognition receptors and are found in the lung and many other tissues including the ET and the middle ear where they probably function in host defense. Surfactant has a potential for use in the treatment of OM due to surface tension lowering function in the ET, and the possible immune functions of SP-D and SP-A in the middle ear and ET.

Expression and Clinical Significance of Various Cytokines in Otitis Media

“…In addition, TLR showed increased or decreased expression depending on the presence of bacteria, disease recurrence, tissue type, and repeat surgery. In conclusion, TLR expression is associated with otitis media, and inappropriate TLR expression, or delayed or absent induction, is associated with the development, recurrence, chronicity, and complications of otitis media [8]. TLR-4 is a host cell expression pattern recognition receptor involved in a variety of functions, including the detection of bacterial endotoxin, with an opposite expression gradient.…”

“…SP-D is an antimicrobial protein that directly inhibits the proliferation of Gram-negative bacteria by increasing the permeability of microbial cell membranes in the form of macrophage phagocytosis and bacterial aggregation [8] [25] [26]. Expression of SP-D was increased in the human middle ear epithelial cell line (HMEEC-1) after attack with lipopolysaccharide in a LPS dose-dependent manner.…”

“…The PRR induces the release and activation of cytokines to promote a range of immune responses to resolve infection. SP-A and SP-D belong to the group of C-type lectins, which function like the PRR and play an important role in host defense and the regulation of pulmonary inflammation [8] [25] [26]. Human SFTPD polymorphisms have been found to have an effect on SP-D protein assembly, function, and concentration and are associated with severe respiratory syncytial virus infections in humans, a known predisposing factor for OM.…”

“…Recent studies have reported the expression of the surface-active proteins SP-A and SP-D in porcine Eustachian tubes, SP-A in rabbit middle ear epithelial cells, and SP-D in rat middle ear epithelial cell lines[10] [25]. (Abdel-Razek et al)[8]…”

Nrf2 orchestrates transition from acute to chronic otitis media through inflammatory macrophages

“…COM is more common in adults, particularly in those with underlying conditions that affect the immune system, such as diabetes (2). The major pathological changes in otitis media include inflammation, fluid buildup, and damage to the middle ear structures (3).…”