Related Experiment Video

Updated: Aug 6, 2026

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

HDAC-driven autophagy repression aids macrophage immune evasion by K. pneumoniae strains displaying classical, MDR,

Kuniyil Abhinand1, Shima Merin Sony1, Avandika B Anil1

  • 1School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kollam, Kerala 690525, India.

Iscience
|July 20, 2026
PubMed

Insights

Multidrug-resistant and hypervirulent Klebsiella pneumoniae evade immune responses by suppressing autophagy via epigenetic reprogramming. Inhibiting histone deacetylases (HDACs) restores autophagy, enhances bacterial clearance, and offers a potential therapeutic strategy.

Area of Science:

  • Immunology
  • Microbiology
  • Epigenetics

Background:

  • Emergence of multidrug-resistant (MDR) and hypervirulent (hvKp) Klebsiella pneumoniae strains presents a significant clinical challenge.
  • Understanding host immune responses to different K. pneumoniae strains is crucial for developing effective treatments.

Purpose of the Study:

  • To compare host epigenetic responses to classical (cKp), MDR-Kp, and hvKp isolates.
  • To investigate the role of histone deacetylases (HDACs) in K. pneumoniae infection and immune evasion.

Main Methods:

  • Infection models using cKp, MDR-Kp, and hvKp isolates.
  • Chromatin immunoprecipitation (ChIP) to analyze HDAC2 enrichment at the ATG5 promoter.
  • Macrophage polarization assays and cytokine expression analysis (IL-10).
  • HDAC1/2 gene knockdown and pharmacological inhibition (CI994, SAHA).

Main Results:

  • All K. pneumoniae strains induced HDAC2 upregulation and H3K18 deacetylation, suppressing autophagy.
  • hvKp induced an immunosuppressive M2-like macrophage phenotype, promoting bacterial survival and IL-10 expression.
  • HDAC inhibition restored autophagy, normalized cytokine responses, enhanced bacterial clearance, and reversed M2 polarization.

Conclusions:

  • HDAC-mediated epigenetic reprogramming is a key mechanism for K. pneumoniae immune evasion.
  • HDAC inhibition represents a promising host-directed therapeutic strategy against K. pneumoniae infections.
Keywords:
Klebsiella pneumoniaeMacrophage polarizationautophagyhistone deacetylaseshost-directed therapymultidrug-resistant strains

More Related Videos

Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-107:32

Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1

Published on: September 5, 2016

Related Concept Videos

Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Atypical Pneumonia01:14

Atypical Pneumonia

Atypical pneumonia, often caused by Mycoplasma pneumoniae, is a form of pulmonary infection that differs from the classical presentation of bacterial pneumonia in both its cause and clinical symptoms. Mycoplasma pneumoniae is a pleomorphic bacterium notable for its lack of a rigid cell wall. This structural characteristic imparts resistance to beta-lactam antibiotics and significantly influences the bacterium’s behavior within the human host.Other pathogens responsible for the disease include...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...