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Modulation of macrophage survival during Klebsiella pneumoniae infections
Nithya N1, Anjoom Mohamed Ali1, Sruthi K P1
1Infection Immunology Lab, National Institute of Technology Calicut, Department of Bioscience and Bioengineering, Kozhikode, India.
Abstract:
Klebsiella pneumoniae, a facultative anaerobe and Gram-negative bacterium, has high clinical significance in public health concerns. K. pneumoniae is given its name in recognition of the German-Swiss microbiologist Edwin Klebs. Carl Friedlander first identified K. pneumoniae as a bacterium isolated from the lungs of individuals who had died from pneumonia. K. pneumoniae is a prominent member of the Enterobacteriaceae family, an opportunistic pathogen, and one of the pathogens sweeping the world in the antibiotic resistance pandemic. This organism accounts for approximately one-third of all Gram-negative infections, including pneumonia, urinary tract infections, liver abscesses, and bacteremia. Classically, these infections commonly occur in individuals who are hospitalized or immunocompromised and regularly treated with β-lactams along with other antibiotics effective against Enterobacteriaceae. Unfortunately, the emergence of multidrug-resistant infections in patients treated at intensive care units (ICUs) has been a serious problem faced by clinicians globally. K. pneumoniae has been recently added to the critical list of microorganisms by the World Health Organization (WHO), highlighting the urgent requirement for new therapeutic options to combat this bacterium. Developing new therapeutic interventions requires a comprehensive understanding of host-pathogen interactions and the role of immune cells in clearing the bacteria. To that end, macrophages play a crucial role in safeguarding our body against infectious agents, as well as contributing to processes such as pathogen clearance and tissue homeostasis. Calcium, a secondary messenger, refines the macrophage protective responses and influences cell survival. Many pathogens have evolved tactics to circumvent the innate immune clearance mechanisms exerted by macrophages. Therefore, this review will focus on the modulation of macrophage innate immune responses and survival upon K. pneumoniae infection.
Insights
Klebsiella pneumoniae, a critical pathogen, drives antibiotic resistance. This review explores how macrophages, vital immune cells, respond to K. pneumoniae infection and how calcium influences these responses for potential new therapies.
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Klebsiella pneumoniae is a significant Gram-negative bacterium causing severe infections like pneumonia and UTIs.
- It is a major contributor to the global antibiotic resistance pandemic, listed as critical by the WHO.
- Multidrug-resistant strains pose a serious threat, especially in intensive care units.
Purpose of the Study:
- To review the modulation of macrophage innate immune responses during Klebsiella pneumoniae infection.
- To understand the role of calcium as a secondary messenger in macrophage survival and protective functions.
- To explore host-pathogen interactions for developing novel therapeutic strategies.
Main Methods:
- Literature review focusing on macrophage responses to Klebsiella pneumoniae.
- Analysis of studies investigating the role of calcium signaling in macrophage immunity.
- Synthesis of information on immune evasion tactics employed by K. pneumoniae.
Main Results:
- Macrophages are crucial for clearing K. pneumoniae and maintaining tissue homeostasis.
- Calcium signaling pathways significantly influence macrophage activation, survival, and effector functions.
- Klebsiella pneumoniae has evolved mechanisms to subvert macrophage-mediated innate immunity.
Conclusions:
- Understanding calcium's role in macrophage responses to K. pneumoniae is vital for new treatment development.
- Targeting macrophage immune responses and calcium signaling may offer novel therapeutic avenues.
- Further research into host-pathogen interactions is needed to combat antibiotic-resistant K. pneumoniae infections.
