A voyage between species to the center of the universe of dendritic cells

Among the myriad immune cells there is one subcategory with singular morphology. These are the dendritic cells, so named because under the microscope they have a star-shaped silhouette with arms having elongated endings. These "pods" or "dendrites" provide a potential area of contact and a range much greater than those of ordinary spherical cells.

The job of dendritic cells is at the heart of the function of the immune system. Able to communicate with virtually all other cells, they coordinate the immune response (to infection, injury, cancer ...) and perform themselves a number of functions (antiviral, for example). In fact, under the term “dendritic cells” hide multiple entities, each specialized in a small number of functions. The cells with which they interact, the signals they receive or the organs in which they reside in part dictate these features.

The team of Marc Dalod is engaged in a long journey in this complex world where much remains to be discovered.

Of mice and men ...

"Dendritic cells orchestrate both the immediate response, that of the ‘spontaneous’ innate immune system but also prepare its later, adaptive, responses, called ‘memory’ in the event that the system meets the same pathogen a second time," says Marc Dalod. "Immunologists are now seeking to better understand the dendritic cell universe because deficiencies in this complex system must sometimes contribute to disease. This is observed in the case of HIV infection, which is significantly less well controlled by our immune system than other viral infections. It is precisely this issue that sparked my interest in this theme: what is wrong with dendritic cells in the immune response to HIV?"

It is never technically easy to study the function of cells in the human body, so the mouse is often the preferred model. However, in order for extrapolation to be relevant, we must first ensure that the cells that are studied and manipulated, in this case the many subfamilies of dendritic cells, are functionally equivalent between the two species.

"Previously, the heterogeneity of dendritic cells was mainly described in mice. Nine types were known: three residents in the organelles specialized in immune functions (e.g. lymph nodes), five nesting in different layers of the skin, the epidermis and dermis, and another population that grows only in inflammatory conditions. You could say that these sub-populations of dendritic cells were different because they weren’t able to produce all of the same antiviral factors (interferon) or they had different labels on their surface”, says Marc Dalod.

"In humans, we did not know as much and equivalence to the dendritic system of the mouse was open to debate. We then tried to unify the model by investigating these cells in greater detail. By mapping them at a precise moment, all the active genes in all human and murine dendritic cells are known. Consequently we have established for the first time convincing homologies between entities not only between tissues within a species but also between two species."

Dendritic cell populations with the same specialization - for example the activation of white blood cells that kill virus - have been described with unprecedented accuracy and found to be equivalent between the spleen and skin in mice, and between mouse and man. This led us to propose a simplified classification of dendritic cells in five subpopulations potentially valid for all tissues and all species.

"We can now use disease models in mice to predict what will be the most effective family of the dendritic cells for protection and then extrapolate these findings to the therapeutic targeting of their human equivalents. Conversely, we can hope to improve a deficient immune response, as in HIV, since we can precisely identify the weakest link”, enthuses Marc Dalod.

... and sheep, pigs, chickens ...

"With the success of this approach, we now will expand our work to the classification of dendritic cells from other animal species. The goal is to better prevent major pandemics of livestock (poultry, lamb, pork ...) and their serious consequences for the economy and human health."

Many applications in human therapy and veterinary medicine may potentially be derived from a fundamental system as complex as the dendritic cells. Most importantly, the small world of dendritic cells alone illustrates the tremendous diversity - morphologies, locations, tissue function, ... of the great family of immune system cells.