Phagosome maturation and modulation of macrophage effector function by intracellular pathogens: target for therapeutics

2021 ◽  
Author(s):  
Brahmaji Sontyana ◽  
Rohini Shrivastava ◽  
Srikanth Battu ◽  
Sudip Ghosh ◽  
Sangita Mukhopadhyay

Macrophages are important cells that regulate various innate functions. Macrophages after engulfment of pathogens proceed for phagosome maturation and finally fuse with lysosomes to kill pathogens. Although pathogen degradation is one of the important functions of phagosomes, various immune-effector functions of macrophages are also dependent on the phagosome maturation process. This review discusses signaling processes regulating phagosome maturation as well as various effector functions of macrophages such as apoptosis, antigen presentation, autophagy and inflammasome that are dependent on the phagosome maturation process. It also discusses strategies adopted by various intracellular pathogens to counteract these functions to evade intracellular destruction mechanisms. These studies may give direction for the development of new therapeutics to control various intracellular infections.

Immunity ◽  
2011 ◽  
Vol 34 (5) ◽  
pp. 807-819 ◽  
Author(s):  
Jackson G. Egen ◽  
Antonio Gigliotti Rothfuchs ◽  
Carl G. Feng ◽  
Marcus A. Horwitz ◽  
Alan Sher ◽  
...  

2020 ◽  
Vol 12 (15) ◽  
pp. 1415-1430
Author(s):  
Jing Qiu ◽  
Shikhar Sharma ◽  
Robert A Rollins ◽  
Thomas A Paul

Immune dysfunction in the tumor microenvironment occurs through epigenetic changes in both tumor cells and immune cells that alter transcriptional programs driving cell fate and cell function. Oncogenic activation of the histone methyltransferase EZH2 mediates gene expression changes, governing tumor immunogenicity as well as differentiation, survival and activation states of immune lineages. Emerging preclinical studies have highlighted the potential for EZH2 inhibitors to reverse epigenetic immune suppression in tumors and combine with immune checkpoint therapies. However, EZH2 activity is essential for the development of lymphoid cells, performing critical immune effector functions within tumors. In this review, we highlight the complexity of EZH2 function in immune regulation which may impact the implementation of combination with immunotherapy agents in clinic.


Blood ◽  
2014 ◽  
Vol 124 (7) ◽  
pp. 1070-1080 ◽  
Author(s):  
Sonia Guedan ◽  
Xi Chen ◽  
Aviv Madar ◽  
Carmine Carpenito ◽  
Shannon E. McGettigan ◽  
...  

Key Points ICOS-based CARs program bipolar TH17/TH1 cells with augmented effector function and in vivo persistence. The expression of selected CAR endodomains can program T cells for their subsequent differentiation fates and effector functions.


2019 ◽  
Vol 113 ◽  
pp. 75-86 ◽  
Author(s):  
Myriam Lawand ◽  
Irini Evnouchidou ◽  
Thomas Baranek ◽  
Sebastian Montealegre ◽  
Sha Tao ◽  
...  

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