Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

Abstract

The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on interand intra-cellular crosstalk important in pulmonary immune responses.

SARS-CoV-2, an Underestimated Pathogen of the Nervous System

“…Moreover, multiple transcriptome studies show and validate ACE-2 expression levels in various non-neuronal cells of olfactory mucosa [97]. Studies support the viral susceptibility of the mucosal cells, sustentacular cells, Bowman's cells, and olfactory stem cells [98,99]. Loss of smell in COVID-19 is marked by potential deterioration of olfactory stem cells and other accessory cells [98].…”

Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model

“…Hence, it must provide the first line of host defense, forming a physicochemical barrier against inhaled toxins, pathogens, allergens and particulates, preventing their entry into the bloodstream [25][26][27]. It also plays an essential role in the mucociliary clearance of foreign matter [28,29] and regulates innate and adaptive immune system responses, prevents inflammation and is involved in tissue remodeling and repair [27,[30][31][32]. The structural integrity of the airway epithelium is provided by apical junction complexes (AJCs) which form highly regulated and selectively permeable barriers between adjacent cells [27,33].…”

Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives

“…The respiratory system is the key interface between the external environment and systemic circulation. It not only allows O 2 /CO 2 gas exchange, but also simultaneously provides a barrier to protect the body from invasion by airborne pathogens and exposure to toxic chemical substances (LeMessurier et al 2020 ). The respiratory system is composed of numerous specialized cell types (Fig.…”

“…It has evolved highly elaborate and effective mechanisms for filtering out, inactivating, and removing foreign materials. These defense mechanisms include mucociliary clearance (MCC) and innate immune capabilities, such as secretion of antimicrobial peptides and cytokines by epithelial cells and resident leukocytes in order to recruit and activate the adaptive immune system (LeMessurier et al 2020 ; Sharma et al 2020 ). Despite these defense mechanisms, the respiratory system remains highly susceptible to direct effects and/or penetration by potentially toxic pathogens, particles, and gases that are commonly encountered in modern environments.…”

“…Examples of various sources of potential damage to the respiratory system include air pollution, occupational exposure to chemicals and particles, and tobacco products, as well as chemicals, fumes, particles, and gas exposures from everyday household chemicals, consumer products, and cosmetics. Additionally, respiratory system-specific pathogens (e.g., influenza, tuberculosis, rhinovirus, and coronaviruses) have evolved and adapted to evade the respiratory defense mechanisms (LeMessurier et al 2020 ; Sharma et al 2020 ). Infection by respiratory bacteria and viruses sickens and kills millions of people worldwide each year as well as inflicts huge economic burdens.…”