Abstract
The lung is a primary organ for gas exchange in mammals that represents the largest epithelial surface in direct contact with the external environment. It also serves as a crucial immune organ, which harbors both innate and adaptive immune cells to induce a potent immune response. Due to its direct contact with the outer environment, the lung serves as a primary target organ for many airborne pathogens, toxicants (aerosols), and allergens causing pneumonia, acute respiratory distress syndrome (ARDS), and acute lung injury or inflammation (ALI). The current review describes the immunological mechanisms responsible for bacterial pneumonia and sepsis-induced ALI. It highlights the immunological differences for the severity of bacterial sepsis-induced ALI as compared to the pneumonia-associated ALI. The immune-based differences between the Gram-positive and Gram-negative bacteria-induced pneumonia show different mechanisms to induce ALI. The role of pulmonary epithelial cells (PECs), alveolar macrophages (AMs), innate lymphoid cells (ILCs), and different pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs) and inflammasome proteins) in neutrophil infiltration and ALI induction have been described during pneumonia and sepsis-induced ALI. Also, the resolution of inflammation is frequently observed during ALI associated with pneumonia, whereas sepsis-associated ALI lacks it. Hence, the review mainly describes the different immune mechanisms responsible for pneumonia and sepsis-induced ALI. The differences in immune response depending on the causal pathogen (Gram-positive or Gram-negative bacteria) associated pneumonia or sepsis-induced ALI should be taken in mind specific immune-based therapeutics.
Highlights
Lungs serve as vital organs for the gaseous exchange in the vertebrates
The potent innate immune response generation in the lungs during localized pulmonary infections or its dysregulation as seen in the non-pulmonary sepsis-associated acute acute lung injury or inflammation (ALI) or acute respiratory distress syndrome (ARDS) plays a crucial role in the disease outcome [12]
NCR1 ligands are expressed by pulmonary macrophages and dendritic cells (DCs), which directly interact with Natural Killer (NK) cells during the early stages of S. pneumoniaeinduced pneumonia (Figure 2B)
Summary
Lungs serve as vital organs for the gaseous exchange in the vertebrates. They have evolved from their very primitive stage (air sacs found in the very primitive and well-armored fossil placoderm fish Bothriolepis) to the most advanced form present in mammals depending on their habitat and the oxygen demand. The recognition of PAMPs or MAMPs and DAMPs involves several pattern recognition receptors (PRRs), including toll-like receptors (TLRs) and multiple germ line encoded receptors [NOD-like receptors (NLRs), retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs) and multiple intracellular DNA sensors expressed (cGAS-STING signaling pathway, Aim 2 like receptors (ALRs)] [8,9,10,11] This induces the pro-inflammatory immune response generating different cytokines, chemokines, interferons (IFNs), and other molecules, including reactive oxygen or nitrogen species (ROS or RNS) for clearing the infection to maintain the immune homeostasis. The potent innate immune response generation in the lungs during localized pulmonary infections (pneumonia) or its dysregulation as seen in the non-pulmonary sepsis (sepsis originating from other sources, including the peritoneum, urinary tract, various soft tissues, and skin)-associated acute ALI or ARDS plays a crucial role in the disease outcome [12]. The major aim of the present article is to describe the pulmonary innate immune response responsible for the ALI observed during bacterial pneumonia and sepsis, as evidenced by both animal and human findings
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
