The role of the innate immune system on pulmonary infections

Abstract

Inhalation is required for respiration and life in all vertebrates. This process is not without risk, as it potentially exposes the host to environmental pathogens with every breath. This makes the upper respiratory tract one of the most common routes of infection and one of the leading causes of morbidity and mortality in the world. To combat this, the lung relies on the innate immune defenses. In contrast to the adaptive immune system, the innate immune system does not require sensitization, previous exposure or priming to attack foreign particles. In the lung, the innate immune response starts with the epithelial barrier and mucus production and is reinforced by phagocytic cells and T cells. These cells are vital for the production of cytokines, chemokines and anti-microbial peptides that are critical for clearance of infectious agents. In this review, we discuss all aspects of the innate immune response, with a special emphasis on ways to target aspects of the immune response to combat antibiotic resistant bacteria.

Keywords: T cells; Toll like receptors; chemokine; cytokines; lung; macrophages.

Figure 1:

Abbreviated examples of innate immune system response in the respiratory epithelium interface to different types of pathogens. (A) Influenza infection: viral particles in the airway lumen are detected by TLR3 and TLR7 in the epithelial cells, triggering an initial response by NF-κβ, activating Type I and II interferons, producing CXCL2 and other chemokines that attract effector cells like macrophages and T cells as well as cytokines, such as IL-1β, IL-17 and IL-18. (B) Klebsiella pneumoniae infection: this Gram-negative bacteria is sensed by TLR2 and TLR3, unfolding a signaling cascade by MyD88, TRIF and NF-κβ, this cascade results in chemokines such as CXCL1, CXCL2 and CXCL5, promoting the recruitment of immune cells and releasing cytokines, most notably, IL-17, IL-6 and TNF-α. (C) Aspergillus fumigatus infection: the airway epithelium detects connidia or hyphae by TLR-2, TLR4 and Dectin-1. Decting-1 activates PCK- , recruiting neutrophils and other immune cells that exert antifungal activity by NADPH and reactive oxygen species (ROS). TLR2 and TLR4 activate PI3K, MAPK and ERK1/2 which results in production of cytokines and chemokines such as IL-8, IL-1α, IL-1β, IL-17, TNF-α, CCL3, CCL4, CxCL1 from the epithelium and immune cells. This response not only contributes to the acute defense of the lung, but also further activate the adaptive immune response.