Jo Experimental & Molecular Medicine (2019) 51:149 https://doi.org/10.1038/s12276-019-0281-8 Experimental & Molecular Medicine

EDITORIAL Open Access Interplay between host and : immune defense and beyond Eun-Kyeong Jo 1,2

Host–pathogen interaction is considered a highly i.e., immune receptors, cytokines, signaling molecules, dynamic process between diverse microbial , and the microbiota. We further describe and hosts in all stages of pathogenic infection, from recent innovative trials based on studies of the invasion to dissemination. Upon pathogenic infection, host–pathogen interface involving the therapeutic utili- innate immune systems respond to pathogen-associated zation of bacteria in the context of anticancer treatments. molecular patterns and activate immediate host inflam- A comprehensive understanding of host–pathogen matory and antimicrobial responses1,2. Innate immune interaction will provide new insights into the identifica- cells trigger sophisticated intracellular signaling pathways tion of novel targets for both host effectors and microbial via innate immune receptors, including membrane-bound factors and will lead to new therapeutic treatments for – or cytosolic receptors1 3. Host innate immune activation infections and other human diseases. results in the production of multiple effector molecules, When encountering the host defense system, numerous including cytokines and chemokines as well as anti- intracellular pathogens employ a variety of evolved stra- microbial proteins, to combat invading pathogens and tegies to escape, modulate, and hijack host immunity parasites4. In addition, innate immune cells, such as during infection9. Lee and coworkers provide a compre- and dendritic cells, are the principal hensive summary of viral strategies that evade host

1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; antigen-presenting cells that activate T cells, which are cytosolic sensing to facilitate intracellular infection and involved in more specific and delicate immune respon- replication of viruses. Although innate immune responses ses5,6. In particular, Th1 cell-mediated (IFN)-γ are essential for combating viral infections, they should be can efficiently promote cell-autonomous host defenses tightly regulated to prevent harmful host responses. Lee against intracellular parasitic and mycobacterial infections and coworkers also review recent findings on the positive through various effectors, including IFN-inducible and negative regulatory mechanisms for intracellular GTPases, inducible nitric oxide synthase, and autophagy sensors in-host cells. Recent studies have uncovered key proteins7,8. signaling molecules that participate in the recognition of Here, a special issue of articles presents recent findings cytosolic pathogen-associated molecular patterns on how host immune and pathological responses are (PAMPs) and the activation of innate immune responses generated by intracellular signaling machinery, which can against viral infection10,11. Ahn and Barber highlight the be activated at various stages of host–pathogen interac- immune regulatory functions of stimulators of interferon tion, and further describes how pathogens subvert host genes and cyclic dinucleotides that can recognize micro- protective responses to establish an infection in the harsh bial DNA from various pathogens, including bacteria, environment inside host cells. In addition, this special viruses, and parasites, as well as cytosolic DNA of self- issue includes invited reviews that discuss current origin from host cells. Investigations on the abundance of knowledge of host defensive components and pathways, in-host effector mechanisms and pathogenic strategies will provide an ideal opportunity to develop innovative tools that can be utilized to modulate microbial Correspondence: Eun-Kyeong Jo ([email protected]) pathogenesis. 1 Department of Microbiology, Chungnam National University School of Autophagy, a cell-autonomous catabolic pathway Medicine, Daejeon 35015, Korea 2Department of Infection Control Convergence Research Center, Chungnam involving lysosomal degradation of cargos, is becoming National University School of Medicine, Daejeon 35015, Korea

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recognized as an innate effector mechanism to enhance with tumor-targeting ability and discuss recent advances pathogen control and resolution of tissue pathology in our understanding of bacterium-tumor cell interactions. – associated with infection12 14. Jo and coworkers sum- In revealing a vast array of strategies adopted by host marize the function of autophagy and xenophagy in cells and pathogens during various stages of infection, mycobacterial infection and how to manipulate autophagy paradigms are shifting. Accumulating evidence indicates a pathways to promote host-targeted therapeutics against more diverse impact of pathogenic manipulations of host mycobacterial infection. A more comprehensive under- cells than previously known. This special issue highlights standing of the elaborate mechanisms by which host recent advances in studies that extend traditional con- autophagy pathways overcome bacterial pathogenesis cepts of host–pathogen interactions toward new insights strategies may lead to more efficient antimicrobial defense on innate and adaptive immune signaling, molecular strategies against numerous intracellular pathogens that pathogenesis, host-directed therapy, and manipulation of – can reside and replicate within the host cell cytoplasm14 16. bacteria for anticancer therapy. We believe that the When considering the role of type I and II cutting-edge reviews presented here will provide novel (IFNs) in the activation of antiviral and Th1 immune insights into the growing area of host–pathogen interface responses, respectively, it is generally accepted that IFN signaling, thereby expanding basic knowledge for use in actions are typically required for protective immune clinical applications. Studying the basic and applied fields responses against viruses and intracellular bacteria. relating to this topic will promote our knowledge of highly Yamamoto and Sasai discuss recent progress on the cell- complex host–pathogen relationships and facilitate future intrinsic defense mechanisms by which IFN-inducible investigations in this area for the development of GTPase-dependent host defenses exhibit antiparasitic and improved therapies against infections. antibacterial responses. IFN-γ-inducible GTPases, Acknowledgements including guanylate binding proteins (GBPs) and This work was supported by the National Research Foundation of Korea (NRF) immunity-related GTPases (IRGs), are essential in various Grant funded by the Korean Government (MSIP; Ministry of Science, ICT & aspects of immune protective functions, including the Future Planning) (2017R1A5A2015385) and by the framework of international cooperation program managed by NRF of Korea (Grant Number: release of bacterial components, production of reactive 2015K2A2A6002008). nitrogen species, inflammasome activation, and autop- 7,8,17,18 hagy . Recent studies have also revealed the function Conflict of interest of cytokines, including type I IFNs, IL-15, and IL-18, in The author declares that she has no conflict of interest. + the bystander activation of CD8 T cells, which are 19,20 responsible for tissue injury in viral infections . Shin Publisher’s note and Kim will present a new concept of bystander Springer Nature remains neutral with regard to jurisdictional claims in response, which leads to pathological or protective out- published maps and institutional affiliations. comes, depending on the context. An understanding of Received: 29 March 2019 Accepted: 19 April 2019 the IFN-inducible responses in various aspects of Published online: 11 December 2019 host–pathogen interactions will be essential for the development of effective therapeutics that also minimize tissue damage. References Accumulating evidence supports the importance of the 1. Beutler, B. Inferences, questions and possibilities in Toll-like receptor signalling. gut microbiota in human health and diseases. Takeda and Nature 430,257–263 (2004). fi 2. Meylan, E., Tschopp, J. & Karin, M. Intracellular pattern recognition receptors in Maeda summarize the recent ndings of molecular details the host response. 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