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A wonderful journey to explore the bacterial world: How do these effector proteins affect the immune system?
In the microscopic world, the presence of bacteria is a double-edged sword for the health of their hosts. As science advances, our understanding grows, especially in how bacteria use specific effector proteins to interact with the host immune system. This article will take you to understand the mechanism of action of these effector proteins, their diversity, and how they affect the host immune response.
Effector proteins are proteins secreted by pathogenic bacteria and enter host cells mainly through three secretion systems.
Function and mechanism of effector proteins
Effector proteins play crucial roles in bacterial pathogenicity. These proteins can help pathogens invade host tissues, suppress the host's immune system, or ensure the survival of pathogens within the host. Some bacteria are able to inject a few effector proteins into host cells, while others may inject dozens or hundreds of different effector proteins.
For example, the plague pathogen (Yersinia pestis) completely loses its pathogenicity if it loses its T3SS, even if it enters the blood directly.
By revealing the diversity of these effector proteins, scientists found that most pathogenic bacteria have the ability to secrete effector proteins. However, the exact number and functions of most pathogens remain poorly understood. Although effector proteins can be predicted through genome sequencing, such predictions are not always accurate, and validating these predictions faces experimental difficulties.
Diversity of effector proteins
For example, some studies of pathogenic Escherichia coli (E. coli) showed that although more than 60 effector proteins were predicted, only 39 were actually confirmed to be secreted into human Caco-2 cells. Within the same bacterial species, different strains often have different repertoires of effector proteins, which further complicates our understanding of their biological significance.
Immune System Interactions
Effector proteins have a wide range of functions, affecting various internal processes of host cells. For example, the T3SS effector proteins of pathogenic Escherichia coli, Shigella, Salmonella, and Yersinia regulate the actin dynamics of host cells, thereby promoting their own attachment or invasion and helping them escape Attack by phagocytes.
Manipulation of the endocytic pathway is critical for bacteria to enter and survive in host cells.
For example, Salmonella is able to manipulate the movement of endosomes to form survival-resistant vesicles (SCVs) required for survival, while Schistosoma japonicum avoids this process by rapidly dissolving its endosomes. This movement and manipulation not only affects the bacteria's ability to survive, but also has a significant impact on the host's immune response.
Regulation of the immune system
Once a pathogen binds to a host cell's receptor, the immune system initiates a series of signaling pathways that lead to the release of cytokines, which regulate the response to infection. Among them, some bacterial effector proteins interact with NF-kB and its signaling pathway to inhibit the host's immune response, thereby helping the pathogens survive successfully in the host.
For example, the effector protein NleC of EPEC/EHEC cleaves the p65 subunit of NF-kB and prevents the production of IL-8.
The functions of these effector proteins are not limited to suppressing immune responses. Some effector proteins can also induce host cell death, thereby promoting bacterial transplantation and proliferation. In addition, the richness and diversity of these effector proteins make the infection strategies of each pathogen different.
Resources and Outlook
As research deepens, more and more databases have been established, such as EffectiveDB and T3DB, enabling researchers to better understand such effector proteins and their potential mechanisms. These resources not only help confirm known effector proteins, but also predict novel ones, facilitating further investigation of these complex interactions.
In summary, bacterial effector proteins play an irreplaceable role in the infection process and they affect the host's immune system in a variety of ways. As our understanding of these effector proteins continues to deepen, will it be possible to develop therapeutics targeting these effector proteins in the future to effectively fight bacterial infections?
