Neutrophil Recruitment in Pneumococcal Pneumonia

Abstract

Streptococcus pneumoniae (Spn) is the primary agent of community-acquired pneumonia. Neutrophils are innate immune cells that are essential for bacterial clearance during pneumococcal pneumonia but can also do harm to host tissue. Neutrophil migration in pneumococcal pneumonia is therefore a major determinant of host disease outcomes. During Spn infection, detection of the bacterium leads to an increase in proinflammatory signals and subsequent expression of integrins and ligands on both the neutrophil as well as endothelial and epithelial cells. These integrins and ligands mediate the tethering and migration of the neutrophil from the bloodstream to the site of infection. A gradient of host-derived and bacterial-derived chemoattractants contribute to targeted movement of neutrophils. During pneumococcal pneumonia, neutrophils are rapidly recruited to the pulmonary space, but studies show that some of the canonical neutrophil migratory machinery is dispensable. Investigation of neutrophil migration is necessary for us to understand the dynamics of pneumococcal infection. Here, we summarize what is known about the pathways that lead to migration of the neutrophil from the capillaries to the lung during pneumococcal infection.

Circadian rhythm disruption in critically ill patients

“…While neutrophils are a crucial part of the host defense, on the other hand, an excessive neutrophil response may be disadvantageous and further aggravate lung injury and lead to systemic bacteriemia 57,58 . In line with this, Ang‐2 (angiotensin‐2), an endothelial mediator known to be increased in patients with severe pneumonia, 59 was found to suppress clock modulator Rev‐Erbα mRNA and protein expression in THP‐1 macrophages in a dose‐ and time‐dependent manner, thereby reducing the production of barrier disrupting enzyme matrix metalloprotease 9 60 .…”

Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response toStreptococcus pneumoniaeinfection

“…with a specific A1 receptor inhibitor (whose specificity we confirmed in prior publications 28,34 ) or vehicle control. Mice were then infected intratracheally with 2.5x10 4 As CXCR2 was reported to be required for trans-endothelial migration in response to pneumococcal infection 11,14,[35][36][37] , we directly assessed the role of A1 on PMN transendothelial migration. Young mice were treated i.p.…”

“…We further found that while A1 receptor inhibition had no effect of CD18 expression (Fig 8C), it significantly lowered CXCR2 expression at 6 hpi (Fig 8D),the time point at which PMN influx to the lungs is lowered (Fig8A). As CXCR2 was reported to be required for trans-endothelial migration in response to pneumococcal infection11,14,[35][36][37] , we directly assessed the role of A1 on PMN trans-endothelial migration. Young mice were treated i.p.…”

Innate Immune Memory in Macrophages

“…250 Memory AMs express major histocompatibility complex (MHC)-II and chemokines at higher levels, and show more glycolysis and bacterial killing. 4,203,[249][250][251] Infection-induced IIM has been associated with molecules such as NOD2; possibly viral RNA; and proteins containing a leucine-rich repeats (LRR)-containing domain are evolutionarily conserved in many proteins associated with innate immunity. 252 Similarly, NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3), which is an intracellular sensor that detects many microbial molecules may also be associated.…”