The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1Œ±
Authors: Xu Shu
Yongkang Lai
Li Tao
Ying Lu
Jianfang Rong
Xiaogang Yuan
Journal: Oxidative Medicine and Cellular Longevity (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CD86; CD206; HIF-1Œ±; gastric mucosa; RAW 264.7 cells
Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006 Jiangxi Province, China., Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006 Jiangxi Province, China., Department of Gastroenterology, Longgang District People's Hospital of Shenzhen, Shenzhen, China.

Abstract:  Methods: The expression of CD86, CD206, and HIF-1Œ± in the gastric mucosa was evaluated through immunohistochemistry. RAW 264.7 cells were cocultured with H. pylori at various multiplicities of infection (MOIs), and iNOS, CD86, Arg-1, CD206, and HIF-1Œ± expression was detected by Western blot, PCR, and ELISA analyses. ROS expression was detected with the fluorescent probe DCFH-DA. Macrophages were also treated with the ROS inhibitor NAC or HIF-1Œ± inhibitor YC-1. Results: Immunohistochemical staining revealed that the macrophage polarization state was associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori affected macrophage polarization, and H. pylori enhanced the expression of ROS and HIF-1Œ± in macrophages. A low MOI of H. pylori promoted both the M1 and M2 phenotypes, while a high MOI suppressed the M2 phenotype. Furthermore, ROS inhibition attenuated HIF-1Œ± expression and switched macrophage polarization from M1 to M2. However, HIF-1Œ± inhibition suppressed ROS expression and inhibited both the M1 phenotype and the M2 phenotype. Inhibition of ROS or HIF-1Œ± also suppressed the activation of the Akt/mTOR pathway, which was implicated in H. pylori-induced macrophage polarization. Conclusions: Macrophage polarization is associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori influences the macrophage polarization state. Crosstalk between ROS and HIF-1Œ± regulates H. pylori-induced macrophage polarization via the Akt/mTOR pathway. 

Retracted: No

PubPeer comments:
 In this study, homeless persons in Marseille were recruited from shelters, examined, and rectal samples were obtained. I have a question about the IRB approval for this study, since homeless persons might be considered to be a  vulnerable population (i.e., vulnerable to coercion), similar to veterans or prisoners in the US, although IRB rules might differ per country. Surprisingly, the IRB approval number listed in this paper (2010-A01406-33) is used for at least 17 studies, including this one. Although all of them involve homeless persons recruited from Marseille shelters, the studies themselves vary in terms of study protocols and treatment sample collection. The studies vary from collecting lice, treating subjects with drug-impregnated underwear, filling out questionnaires, medical exams, to nasal and pharyngeal sampling, skin swabbing, blood draw, rectal samples, sputum collection, and chest X rays. Moreover, the studies were performed from 2011 to 2020, spanning almost 10 years. Would the authors be willing to share the original 2010 ethical approval application here? Did they get approval for all these different studies spanning 10 years, in one single application? There is also confusion about which institution or ethical board approved the study. Some papers state that the study was approved by  our institutional review board , suggesting that this was a number referring to IRB approval by the Aix-Marseille Universitu00e9 and or Institut Hospitalo-Universitaire Mu00e9diterranu00e9e Infection, both listed as author affiliations. But in other papers, the IRB approval number appears to be an ANSM RCB authorization ID, as per  Informed consent was obtained from these subjects, and the study was approved by the u2018u2018Comitu00e9 de Protection des Personnes Sud Mediterranu00e9eu2019u2019 on January, 12, 2011 (ID RCB: 2010-A01406-33) , e.g. as mentioned in PLoS ONE 8(2): e58088. Either way, it would be of interest to take away any concern whether studies on this vulnerable populations were all performed within the original IRB approval scope. Here is the list of 17 papers that all appear to share the same ethical approval number: * Rezak Drali et al. - Journal of Clinical Microbiology (2012) p. 2229u20132233 - DOI: 10.1128 JCM.00808-12 * Rezak Drali et al. - PLoS ONE 8(2): e58088 (2013) - DOI: 10.1371 journal.pone.0058088 * Samir Benkouiten et al. - JAMA Dermatol. 2014;150(3):273-279 (2014) - DOI: 10.1001 jamadermatol.2013.6398 * Rezak Drali et al - Infection, Genetics and Evolution 39 (2016) 225u2013231 - DOI: 10.1016 j.meegid.2016.02.008 * Tran Duc Anh Ly et al. - Emerging Infectious Diseases (2017) - DOI: 10.3201 eid2311.170516 * Tran Duc Anh Ly et al. - Clinical Microbiology and Infection 25 (2019) 249.e1e249.e6 - DOI: 10.1016 j.cmi.2018.04.032 * Tran Duc Anh Ly et al. - Front. Cell. Infect. Microbiol. 9:86 (2019) - DOI: 10.3389 fcimb.2019.00086 * Tran Duc Anh Ly et al. - Journal of Epidemiology and Global Health (2019) - DOI: 10.2991 jegh.k.190510.001 * Tran Duc Anh Ly et al. - Infection and Drug Resistance 2019:12 1139u20131151 - DOI: 10.2147 IDR.S202048 * Nadia Amanzougaghene et al. - Parasites Vectors (2020) 13:177 - DOI: 10.1186 s13071-020-04036-y * Tran Duc Anh Ly et al. - European Journal of Clinical Microbiology Infectious Diseases (2020) - DOI: 10.1007 s10096-020-03889-6 * Tran Duc Anh Ly et al. - Travel Medicine and Infectious Disease 36 (2020) 101768 - DOI: 10.1016 j.tmaid.2020.101768 * Tran Duc Anh Ly et al. - Vector-Borne and Zoonotic Diseases (2020) - DOI: 10.1089 vbz.2019.2603 * Tran Duc Anh Ly et al. - Acta Microbiologica et Immunologica Hungarica (2021) - DOI: 10.1556 030.2021.01346 * Tran Duc Anh Ly et al. - Journal of Epidemiology and Global Health (2021) - DOI: 10.2991 jegh.k.201009.001 * Tran Duc Anh Ly et al. - Journal of Infection Volume 82, Issue 1, January 2021, Pages 60-66 - DOI: 10.1016 j.jinf.2020.11.026 * Tran Duc Anh Ly et al. - European Journal of Clinical Microbiology Infectious Diseases (2021) - DOI: 10.1007 s10096-020-04127-9 ,