Leukocytes migrating in lymph from the oro-nasal mucosae : interest for vaccination and immune tolerance

We developed a novel sheep model of lymphatic catheterisation to collect, in real time, cells circulating in the afferent lymph draining mainly the mucosae in the head. With this model, we were able to collect migrating leukocytes, either in their baseline condition, or after the administration of a vaccine antigen, from the oro-nasal mucosa to the draining lymph nodes where the immune response takes place. We showed that particulate antigens, such as bacteria, are taken from the tissues to the lymph nodes mainly by two types of cells, the monocytes and the granulocytes, and only occasionally by dendritic cells (DC). This finding challenges the general view, common among immunologists, whereby dendritic cells capture the antigen in the tissues before taking it to the lymph node. In addition, our study identified the permanent migration of a subset of DC - expressing the CD26 molecule – which carries cell-derived apoptotic bodies of self. This DC subset could be responsible for self-tolerance, a mechanism involved in control of transplant rejection, autoimmune diseases and vaccination.Un modèle original de cathétérisme lymphatique chez l'ovin, développé dans notre laboratoire, permet d'accéder en temps réel aux cellules en migration dans la lymphe drainant principalement les muqueuses de la tête de l'animal. Ainsi, à l'état basal ou après administration d'un antigène vaccinal, il est possible de collecter des cellules leucocytaires migrant depuis les muqueuses oro-nasales vers les ganglions, sites décisionnels de la réponse immune. Grâce à ce modèle, nous avons montré que des antigènes particulaires, notamment des bactéries, étaient transportés dans la lymphe essentiellement par deux types de cellules, les monocytes et les granulocytes et plus marginalement par les cellules dendritiques (DC). Ces résultats modifient la vision linéaire communément admise selon laquelle les DC capturent, transportent et présentent les antigènes aux lymphocytes naïfs; ils suggèrent que d'autres populations phagocytaires, impliquées dans le transport antigénique, pourraient moduler la réponse immune. Par ailleurs, nous avons mis en évidence la migration permanente d'une sous-population de DC, identifiée par la molécule CD26, qui transporte des débris de cellules du soi. Ce phénomène pourrait être impliqué dans la tolérance périphérique, mécanisme d'importance dans le rejet des greffes, les maladies auto-immunes et la vaccination

An in vitro model to assess the immunosuppressive effect of tick saliva on the mobilization of inflammatory monocyte-derived cells

Tick-borne pathogens cause potent infections. These pathogens benefit from molecules contained in tick saliva that have evolved to modulate host innate and adaptive immune responses. This is called "saliva-activated transmission" and enables tick-borne pathogens to evade host immune responses. Ticks feed on their host for relatively long periods; thus, mechanisms counteracting the inflammation-driven recruitment and activation of innate effector cells at the bite site, are an effective strategy to escape the immune response. Here, we developed an original in vitro model to evaluate and to characterize the immunomodulatory effects of tick saliva that prevent the establishment of a local inflammatory immune response. This model mimics the tick bite and enables the assessment of the effect of saliva on the inflammatory-associated dynamic recruitment of cells from the mononuclear phagocyte system. Using this model, we were able to recapitulate the dual effect of tick saliva on the mobilization of inflammatory monocyte-derived cells, i.e. (i) impaired recruitment of monocytes from the blood to the bite wound; and (ii) poor mobilization of monocyte-derived cells from the skin to the draining lymph node. This simple tool reconstitutes the effect of tick saliva in vivo, which we characterized in the mouse, and should enable the identification of important factors facilitating pathogen infection. Furthermore, this model may be applied to the characterization of any pathogen-derived immunosuppressive molecule affecting the establishment of the inflammatory immune response

Challenges and Opportunities of a Mucosal Platform for Nasal Vaccination

International audienc

Caractérisation biochimique de la variabilité des populations du puceron pois : Acyrthosiphon pisum (Harris)

*INRA, Laboratoire de zoologie, 86600 Lusignan (FRA) Diffusion du document : INRA, Laboratoire de zoologie, 86600 Lusignan (FRA) Diplôme : Maîtris

Vaccins Covid : Les différents types, comment ils agissent ?

National audienc

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy. ATTACK Cellular Therapy of Cancer Symposiu

Bovine innate immunity against Mycobacterium bovis

National audienc

Reconstitution d'un modèle d'alvéole pulmonaire à partir de cellules primaires bovines pour étudier la physiopathologie de la tuberculose

Reconstitution d'un modèle d'alvéole pulmonaire à partir de cellules primaires bovines pour étudier la physiopathologie de la tuberculose. 4. Conférence du MycoClu

How to obtain crystal clear organ with a clearing procedure

National audienc

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy

Different conditioning protocols result in distinct lymphopenic environments: consequences for regulatory T cells and anti-tumor immunotherapy. Annual Meeting of the French Society for Immunolog