Related Experiment Video
Updated: Apr 7, 2026
Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection
Katharine Orf1, Aubrey J Cunnington1
1Section of Paediatrics, Imperial College London London, UK.
Abstract:
Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk.
Insights
Malaria and Oroya fever increase susceptibility to bacterial co-infections like Salmonella. Hemolysis impairs neutrophil function, creating a niche for bacterial growth and increasing mortality risk.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Malaria and Oroya fever are associated with increased risk of co-infection with enteric Gram-negative bacteria.
- Epidemiological data suggest a causal link between these infections and bacterial co-infections, not just shared risk factors.
- Both diseases involve hemolysis, which is implicated in the increased susceptibility to bacterial co-infections.
Purpose of the Study:
- To critically appraise and summarize the evidence for mechanisms underlying susceptibility to bacterial co-infections in malaria and Oroya fever.
- To propose potential interventions to mitigate the risk of these co-infections.
Main Methods:
- Review and synthesis of existing epidemiological and animal model data.
- Analysis of host defense mechanisms impaired by hemolysis.
- Investigation of the role of heme oxygenase-1 in neutrophil dysfunction.
Main Results:
- Hemolysis impairs crucial host defense mechanisms, including macrophage and neutrophil function, and adaptive immunity.
- Heme oxygenase-1 induction in bone marrow dysregulates neutrophil oxidative burst capacity.
- Dysfunctional neutrophils serve as a niche for intracellular bacterial replication.
Conclusions:
- Hemolysis-induced neutrophil dysfunction is a key mechanism contributing to bacterial co-infections in malaria and Oroya fever.
- Understanding these mechanisms can guide the development of interventions to reduce co-infection risks and improve patient outcomes.
More Related Videos
Related Concept Videos
01:26Factors Affecting the Risk of Infection
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
01:01Hypersensitivity Reactions: Cytolytic Reactions
01:26Healthcare Associated Infections I: Iatrogenic, Exogenic and Endogenic
HAIs significantly increase the cost of health care. Extended stays in healthcare institutions, increased disability, increased costs of medications, including specialized antibiotics, and prolonged recovery times add to the patient's expenses and the healthcare institution and funding bodies.
01:31Defense Against Bacterial Pathogens
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...
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...