Article
Immunology
Su Jeong Lee, Bo Ruem Yoon, Hee Young Kim, Su-Jin Yoo, Seong Wook Kang, Won-Woo Lee
Summary: The study demonstrates that activated platelets induce CD16 expression on classical CD14(+)CD16(-) monocytes through soluble factors, contributing to antibody-dependent cellular phagocytosis (ADCP). CD14(+)CD16(-) monocytes treated with activated platelets preferentially differentiate into M2 macrophages, and elevated levels of the activated platelet marker sCD62P are found in plasma of rheumatoid arthritis patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Yoann Rombouts, Olivier Neyrolles
Summary: This study reveals that Mycobacterium tuberculosis produces a virulence factor called 1-tuberculosinyladenosine, which leads to lysosomal dysfunction and lipid accumulation in macrophages similar to lysosomal storage diseases. These findings provide insights into how the bacteria manipulates host lipid metabolism for its survival and suggest new strategies for host-directed therapy against tuberculosis.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Microbiology
Khushboo Borah Slater, Luana Moraes, Ye Xu, Daniel Kim
Summary: In this study, the authors used C-13 metabolic flux analysis to measure intracellular carbon metabolic fluxes in Mtb-infected macrophages and found that glycolytic fluxes were significantly increased and pentose phosphate pathway fluxes were reduced in infected macrophages.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elena G. Ufimtseva, Natalya I. Eremeeva, Tatiana V. Umpeleva, Diana V. Vakhrusheva, Sergey N. Skornyakov
Summary: The study compared Mtb loads in different lung lesions of TB patients and identified tuberculoma walls as the main niche for Mtb survival. Understanding the host-pathogen interactions is crucial for developing new therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Leah Isobella Rankine-Wilson, Tirosh Shapira, Carine Sao Emani, Yossef Av-Gay
Summary: Tuberculosis, caused by Mycobacterium tuberculosis, is a serious disease that requires lengthy and complicated treatment. Understanding the physiological mechanisms of Mtb can lead to the development of more effective drug therapies.
Article
Microbiology
Patrick Niekamp, Gaelen Guzman, Hans C. Leier, Ali Rashidfarrokhi, Veronica Richina, Fabian Pott, Caroline Barisch, Joost C. M. Holthuis, Fikadu G. Tafesse
Summary: Phagocytosis by alveolar macrophages is the initial step in Mycobacterium tuberculosis (Mtb) infection. The process relies on an intact sphingolipid biosynthetic pathway, where disruption leads to reduced pathogen uptake. This pathway is crucial for the segregation of regulatory molecules and downstream activation of signaling molecules, highlighting a potential target for antimycobacterial therapeutics.
Review
Immunology
Poornima Sankar, Bibhuti Bhusan Mishra
Summary: Tuberculosis remains a global health challenge, causing a significant number of deaths every year. The interaction between Mycobacterium tuberculosis and innate immune cells, such as macrophages and dendritic cells, plays a crucial role in the host defense against the infection. However, our understanding of these interactions is still limited. This review focuses on exploring the early host-pathogen interactions and the contribution of various innate immune cells and mucosal barrier in tuberculosis immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Weifeng Gao, Yurong Cai, Gang Zhang, Xiaoping Wang, Juan Wang, Yong Li, Yujiong Wang
Summary: This study used dual lipidomics to uncover the differences in lipid composition between Mycobacterium tuberculosis and Mycobacterium bovis, as well as the lipid metabolism responses in primary bovine alveolar macrophages infected by these bacteria. The results showed significant differences in various lipid categories between the two species and revealed distinct lipid metabolism responses in host macrophages. The findings suggest that the differential lipid compositions enable the successful colonization and development of the bacteria in macrophages through different mechanisms.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Qianqian Xing, Youxin Feng, Haimei Sun, Shu Yang, Tingyi Sun, Xiaoxia Guo, Fengqing Ji, Bo Wu, Deshan Zhou
Summary: The study demonstrated that MARCO plays an important role in the phagocytosis of tumor cells by macrophages. MARCO expression was correlated with macrophages' ability to carry out phagocytosis.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Plant Sciences
Fei He, Fengjuan Gao, Nan Cai, Min Jiang, Chao Wu
Summary: This study found that CGA enhances alveolar macrophages phagocytosis by upregulating GPR37 expression, thus attenuating lung inflammatory injury.
Article
Microbiology
Hylton E. Rodel, Isabella A. T. M. Ferreira, Carly G. K. Ziegler, Yashica Ganga, Mallory Bernstein, Shi-Hsia Hwa, Kievershen Nargan, Gila Lustig, Gilla Kaplan, Mahdad Noursadeghi, Alex K. Shalek, Adrie J. C. Steyn, Alex Sigal
Summary: Aggregated Mtb infection leads to upregulation of pro-inflammatory genes and enhanced TNF alpha signaling via the NF kappa B pathway in human macrophages. Phagocytosis of Mtb aggregates leads to decreased acidification and increased cell death, suggesting a potential mechanism for TB pathogenesis. Detection of Mtb aggregates in patient granulomas raises the possibility of increased inflammation, bacterial growth, and macrophage death, leading to active disease and transmission cycles.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Sebastian F. Zenk, Sebastian Hauck, Daniel Mayer, Mark Grieshober, Steffen Stenger
Summary: Hypoxia-inducible factor (HIF) plays a crucial role in regulating cellular metabolism in response to a low oxygen environment, and stabilizing HIF can enhance host antimicrobial activity against tuberculosis. Inhibition of prolyl-hydroxylases by Molidustat further induces specific immune effectors, reducing the proliferation of intracellular mycobacteria in human macrophages. These findings suggest that HIFs may be promising targets for host-directed therapy against infectious diseases like tuberculosis caused by intracellular bacteria.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Reiner Noschka, Fanny Wondany, Gonul Kizilsavas, Tanja Weil, Gilbert Weidinger, Paul Walther, Jens Michaelis, Steffen Stenger
Summary: Gran1, a synthetic fragment of Granulysin, demonstrates efficient antimicrobial activity against Mycobacterium tuberculosis and clinically relevant non-tuberculous mycobacteria. It interacts with the surface of Mtb, causing lethal distortions of the cell wall, while showing no off-target effects in primary human cells or zebrafish embryos. Gran1 is selectively internalized by macrophages, restricting the proliferation of the pathogen, and its hypothesis-driven design serves as a powerful approach for identifying small bioactive compounds with specific antimicrobial activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jie Zhou, Fang Fang, Jinying Qi, Tengteng Li, Lin Zhang, Hui Liu, Jingzhu Lv, Tao Xu, Fengjiao Wu, Chuanwang Song, Wei Li, Xiaojing Wang, Xianyou Chang, Hongtao Wang, Ting Wang, Zhongqing Qian
Summary: Tuberculosis is a global threat to public health, and Nrf2 plays a key role in regulating protective immunity against mycobacterial infection. The expression of Nrf2 protein increases after M. tuberculosis infection, while the expression of Keap1 protein remains low. The activation of Nrf2 by SFN reduces inflammation, increases ROS levels, promotes autophagy, and enhances bacterial killing by macrophages.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Microbiology
Pierre Santucci, Beren Aylan, Laure Botella, Elliott M. Bernard, Claudio Bussi, Enrica Pellegrino, Natalia Athanasiadi, Maximiliano G. Gutierrez
Summary: This study investigates the effect of intracellular environments on the efficacy of antibiotics against Mycobacterium tuberculosis. By using a dual live imaging approach, the researchers found that intracellular acidification is a prerequisite for the antibacterial efficacy of pyrazinamide, a first-line anti-TB drug.
Article
Cardiac & Cardiovascular Systems
Tom J. O'Donohoe, Ryan G. Schrale, Suchandan Sikder, Nuzhat Surve, Donna Rudd, Natkunam Ketheesan
HEART LUNG AND CIRCULATION
(2019)
Letter
Immunology
Suchandan Sikder, Catherine M. Rush, Brenda L. Govan, Robert E. Norton, Madeleine W. Cunningham, David J. McMillan, Kadaba S. Sriprakash, Natkunam Ketheesan
JOURNAL OF INFECTIOUS DISEASES
(2019)
Article
Cell Biology
Suchandan Sikder, Catherine M. Rush, Brenda L. Govan, Md A. Alim, Natkunam Ketheesan
JOURNAL OF LEUKOCYTE BIOLOGY
(2020)
Article
Immunology
Mohammad Abdul Alim, Andreas Kupz, Suchandan Sikder, Catherine Rush, Brenda Govan, Natkunam Ketheesan
MICROBES AND INFECTION
(2020)
Article
Multidisciplinary Sciences
Harindra D. Sathkumara, Visai Muruganandah, Martha M. Cooper, Matt A. Field, Md Abdul Alim, Roland Brosch, Natkunam Ketheesan, Brenda Govan, Catherine M. Rush, Lars Henning, Andreas Kupz
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Microbiology
Harindra D. Sathkumara, Karyna Hansen, Socorro Miranda-Hernandez, Brenda Govan, Catherine M. Rush, Lars Henning, Natkunam Ketheesan, Andreas Kupz
Summary: There is a difference in the efficacy of MET against tuberculosis in diabetic and nondiabetic individuals, which warrants further investigation.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Jodie L. Morris, Brenda L. Govan, Catherine M. Rush, Natkunam Ketheesan
Summary: Patients with type 2 diabetes are 10 times more likely to develop bacterial infections, specifically melioidosis caused by Burkholderia pseudomallei, due to dysregulated early immune responses making them more susceptible to the infection.
MICROBES AND INFECTION
(2021)
Article
Microbiology
Nuzhat Z. Surve, Prafulla G. Kerkar, Chandrahas T. Deshmukh, Milind Y. Nadkar, Preeti R. Mehta, Natkunam Ketheesan, Kadaba S. Sriprakash, Mohan G. Karmarkar
Summary: The study revealed elevated antibody responses against host tissue proteins in ARF/RHD patients, with different kinetics of antibody responses against S2 peptides between patient groups, indicating their potential use as markers for monitoring cardiac damage in patients with ARF/RHD.
JOURNAL OF MEDICAL MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yun Heacock-Kang, Ian A. McMillan, Michael H. Norris, Zhenxin Sun, Jan Zarzycki-Siek, Andrew P. Bluhm, Darlene Cabanas, Robert E. Norton, Natkunam Ketheesan, Jeff F. Miller, Herbert P. Schweizer, Tung T. Hoang
Summary: Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations. The authors develop a 'TRANSITomic' approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection, revealing dynamic gene-expression flux during transit in host cells and identifying genes that are required for pathogenesis. The 'TRANSITome' approach enables high-resolution understanding of host-pathogen interactions.
NATURE COMMUNICATIONS
(2021)
Article
Cardiac & Cardiovascular Systems
David J. McMillan, Rukshan A. M. Rafeek, Robert E. Norton, Michael F. Good, Kadaba S. Sriprakash, Natkunam Ketheesan
Summary: The current diagnosis of ARF/RHD relies on clinical observations and non-specific laboratory tests, but advancements in technology have allowed for the potential identification of pathogen associated peptides specific to ARF/RHD. Collaboration and sharing of patient samples could facilitate the development of specific tests, and appropriate animal models may help determine the pathognomonic nature of these peptides. Identification of such peptides could aid in testing potential vaccines and developing affordable point of care devices.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Rukshan A. M. Rafeek, Suchandan Sikder, Adam S. Hamlin, Nicholas M. Andronicos, David J. McMillan, Kadaba S. Sriprakash, Natkunam Ketheesan
Summary: The pathogenesis of ARF/RHD and associated neurobehavioral complications is complex, and robust animal models are required to understand the disease mechanisms. Though challenging, rodent models have significantly contributed to this area, with the Lewis rat autoimmune valvulitis model showing similarities to ARF/RHD.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Rukshan A. M. Rafeek, Catherine M. Lobbe, Ethan C. Wilkinson, Adam S. Hamlin, Nicholas M. Andronicos, David J. McMillan, Kadaba S. Sriprakash, Natkunam Ketheesan
Summary: The study identified a new animal model that can simultaneously investigate the neurobehavioral and cardiac abnormalities associated with post-streptococcal complications. Among different strains and genders of rats, Lewis rats exhibited behavioral and cardiac pathology changes more consistent with clinical presentations, making them an important tool for future research.
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Harindra D. Sathkumara, Janet L. Eaton, Matt A. Field, Brenda L. Govan, Natkunam Ketheesan, Andreas Kupz
Summary: Tuberculosis is one of the deadliest infectious diseases globally, and type 2 diabetes significantly increases the risk of developing active TB. Recent evidence shows that the microbiota plays a significant role in host response to infection, injury, and neoplastic changes. Animal models are crucial for assessing new treatments and understanding immunological defects in comorbid patients with increased TB susceptibility.
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
(2021)
Article
Oncology
Agnieszka Beata Malczewski, Severine Navarro, Jermaine I. G. Coward, Natkunam Ketheesan
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Immunology
Harindra D. Sathkumara, Saparna Pai, Michel de Jesus Aceves-Sanchez, Natkunam Ketheesan, Mario Alberto Flores-Valdez, Andreas Kupz
FRONTIERS IN IMMUNOLOGY
(2019)