The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to  Infection with Legionella pneumophila or Streptococcus pyogenes

Gamradt P, Xu Y, Gratz N, Duncan K, Kobzik L, Högler S, Kovarik P, Decker T, Jamieson AM.

PLoS Pathog. (2016) 12(12):e1006032

 Speaker: An-Chi Gu (顧安琪)                                       Time: 14:00~15:00, Oct. 18, 2017

 Commentator: Dr. Bei-Chang Yang (楊倍昌老師)         Place: Room 601

Abstract:

The immune system protects from infections primarily by detecting and eliminating the invading pathogens, however, the host organism can use another strategy to protect itself by reducing the negative impact of infections on host fitness called tolerance/resilience. (1). Myeloid cells play important roles in innate immune, they are essential in direct phagocytosis and destruction of pathogens, and activation of other immune cells by secretion of cytokines and chemokines (2). Both the immune response and pathogens themselves can cause damage to the infected host, so immune system must be carefully controlled to prevent excessive damage (3). One mechanism of both controlling pathogen replication and host inflammation is programmed cell death (PCD). Myeloid cells will undergo programmed cell death to prevent excessive inflammation once pathogen is cleared. In this study, authors developed a mouse model with decreased myeloid cell death and used two bacterial pathogen, L. pneumophila and S. pyogenes, to understand the balance between controlling pathogen clearance and maintaining host resilience during in vivo infections. The results showed that the transgenic mice infected with L. pneumophila lead to increased inflammation and immune cells infiltrated into the lung. However, both littermate and transgenic mice colud survive and clear the infection. During infection with S. pyogenes, transgenic mice had significant increase in inflammation both at the infection site and systemically. Besides, transgenic mice significantly decreased survival compared to littermate controls, it suggested that host resilience to systemic S. pyogenes infection was compromised by decreased myeloid cell death due to an excessive inflammatory response. This study demonstrated tight regulation of PCD in myeloid cells , and how important it was for host resilience. There were other pathways compensating for the increase in inflammation and prevented a large decrease in host resilience during lung infection. In contrast, during a systemic infection decreased PCD and consequently increased inflammation overwhelmed the host and lead to decreased resilience as indicated by survival.

References:

1.      Ruslan Medzhitov, David S. Schneider, and Miguel P. Soares. (2012). Disease Tolerance as a Defense Strategy. Science. 335, 936–941.

2.      Shi C, Pamer EG. (2011). Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 11, 762-774.

3.      Chovatiya R, Medzhitov R. (2014). Stress, Inflammation, and Defense of Homeostasis. Mol Cell. 54,  281-288.