Page 71 - MI-2-1

Microbes & Immunity Copper and cuproptosis in immunity

Figure 1. Schematic representation of bacterial pathogens in the context of host-pathogen interaction. This figure illustrates the copper transport,
efflux, induction, and resistance pathways within selected bacterial pathogens, namely the Gram-positive Streptococcus pneumoniae and Mycobacterium
tuberculosis, as well as the Gram-negative Escherichia coli and Salmonella. Notably, whereas the Gram-negative bacteria are characterized by a more
prominent periplasmic space, which is integral to their copper handling and other physiological processes, the Gram-positive bacteria, despite having a
relatively less conspicuous periplasmic region (as indicated by shading and annotated in the legend), also partake in these mechanisms.

absence of MctB, the bacterium becomes vulnerable to similarities and distinct differences when compared
copper overload, which jeopardizes its survival. to other diseases. One of the primary roles of copper in
The coordination of copper homeostasis in immune function is its influence on antimicrobial activities.
M. tuberculosis is further regulated by copper-inducible During infection, elevated copper levels can stimulate
proteins, including CosR, which modulate intracellular immune responses, aiding in pathogen resistance. This
copper concentrations. Under conditions of excess heightened copper concentration is integral to the innate
copper, M. tuberculosis initiates the expression of MymT immune response, as it acts as a signaling molecule that
to sequester the surplus copper, followed by expulsion regulates the kinase activity of α-kinase 1, enhancing
64
through the action of CptV and MctB. This finely tuned the host’s ability to respond to bacterial infections. In
63
regulation of copper ions not only contributes to bacterial addition, copper mediates various cell death pathways that
resilience against host defenses but also reinforces the can influence the fate of immune cells, particularly under
pathogen’s overall virulence. conditions of infection. For example, copper-induced cell
death, referred to as cuproptosis, can lead to immune cell
6. Similarities and differences in apoptosis in certain contexts, thereby shaping the overall
cuproptosis and related gene networks: inflammation and immune response. 65
Infection immunity versus other diseases The metabolic abnormalities associated with copper

The metal’s involvement in immune responses is can lead to the accumulation of ROS, which are critical
characterized by its ability to modulate the function of mediators in many pathological conditions, including
immune cells, particularly white blood cells, thereby infections, cancer, and neurodegenerative diseases. ROS
promoting antimicrobial effects (Figure 2). For instance, not only influences immune responses but also modulates
copper enhances the bactericidal capacity of macrophages, cellular signaling pathways and gene expression. Notably,
bolstering the host’s defenses against pathogens. However, the generation of ROS can differ vastly between infectious
the relationship between copper, cell death mechanisms, and non-infectious conditions, impacting cellular outcomes
and infection immunity is complex, demonstrating both of stress and damage. Despite its essential role in enhancing

Volume 2 Issue 1 (2025) 63 doi: 10.36922/mi.5657