M cells, also known as microfold cells, are a specialized cell type found within the lining of the gut. Their unique name, “microfold,” refers to their distinct surface appearance, which differs from the typical finger-like projections of other intestinal cells. These cells serve a specific function within the immune system, acting as a bridge between gut contents and underlying immune cells. This allows them to recognize and respond to various substances in the digestive tract.
Location and Structure
M cells are primarily located in specialized structures within the small intestine called Peyer’s patches, which are part of the gut-associated lymphoid tissue (GALT). They are situated within the follicle-associated epithelium, the thin layer of cells covering these lymphoid follicles. Their strategic placement allows them to directly interact with the gut lumen.
M cells have a distinct structure compared to surrounding intestinal cells. Unlike typical intestinal epithelial cells (enterocytes) that have numerous, uniform microvilli, M cells possess short, irregular microvilli or even lack these protrusions on their apical surface, the side facing the gut contents. This unique “microfold” appearance allows for easier access to the intestinal lumen.
A defining structural feature of M cells is a deep, pocket-like invagination on their basolateral surface, the side facing away from the gut lumen. This pocket provides a sheltered space for various immune cells, including lymphocytes (such as B and T cells), macrophages, and dendritic cells. The close proximity of M cells to these immune cells is fundamental to their role in immune surveillance.
Mechanism of Action
M cells perform their primary function through a process called antigen sampling, where they take up various substances from the gut lumen, such as bacteria, viruses, toxins, and food particles. These substances are referred to as antigens. Their modified apical surface, with sparse microvilli and a thinner glycocalyx, facilitates this uptake.
The uptake of antigens by M cells can occur through different mechanisms, including endocytosis, phagocytosis, or receptor-mediated intake. Once engulfed, these antigens are encased in vesicles within the M cell cytoplasm. The cell then transports these vesicles across its body, from the apical side to the basolateral pocket, in a process known as transcytosis.
Upon reaching the basolateral pocket, the M cell releases the sampled antigens into underlying immune cells, such as dendritic cells and lymphocytes. These immune cells then process the antigens and can present them to other immune cells, initiating an appropriate immune response. This direct delivery system allows for rapid communication between the gut environment and the underlying immune system.
Immune System Significance
M cells play a significant role in shaping the gut’s immune responses. Their ability to sample antigens directly contributes to the development of protective immunity. By presenting antigens to underlying immune cells, M cells help trigger responses like the production of secretory IgA (SIgA), a type of antibody that helps neutralize pathogens in the gut. This targeted delivery allows the immune system to recognize and respond to potentially harmful invaders.
Beyond protective responses, M cells also contribute to oral tolerance, a process where the immune system learns to ignore harmless substances, such as food antigens and beneficial commensal bacteria, preventing unnecessary inflammatory reactions. The precise mechanisms by which M cells differentiate between harmful pathogens and harmless substances are complex, involving selective recognition and interaction with different microbial components.
Despite their beneficial role in immune surveillance, M cells can also be exploited by certain pathogens as a “gateway” to infect the host. Bacteria like Salmonella, Shigella flexneri, and Yersinia, as well as viruses such as poliovirus and reovirus, have evolved strategies to use M cells for entry into the body. This highlights a dual aspect of M cell function, serving both as a protective sentinel and a potential point of vulnerability in the gut’s defenses.