Skin microbiota dynamics following B. subtilis formulation challenge: an in vivo study in mice.

BACKGROUND: Modulating the microbiota is a leading-edge strategy for the restoration and maintenance of a healthy, balanced environment. The use of health-promoting bacteria has demonstrated some potential benefits as an alternative for skin microbiota intervention. Here, we investigate the manipulation of mice skin microbiota using B. subtilis incorporated into a supportive Pluronic F-127 hydrogel formulation. The formula plays an important role in delivering the bacteria to the desired action site. RESULTS: The B. subtilis challenge induced a shift in the composition and abundance of the skin microbiota. Containment of B. subtilis in the Pluronic F-127 hydrogel accelerated bacterial modulation compared with free B. subtilis. The abundance of both Staphylococcus and Corynebacterium spp. was altered as a result of the live bacterial intervention: the abundance of Corynebacterium increased while that of Staphylococcus decreased. Four days after last application of the B. subtilis formulation, B. subtilis counts returned to its initial level. CONCLUSIONS: B. subtilis intervention can induce a shift in the skin microbiota, influencing the abundance of commensal, beneficial, and pathogenic bacteria. Containment of B. subtilis in Pluronic hydrogel accelerates the microbial alteration, probably by facilitating bacterial attachment and supporting continuous growth. Our results reveal the ability of B. subtilis in Pluronic to modulate the skin microbiota composition, suggesting that the formulation holds therapeutic potential for skin disease treatment.

Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface.

Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal the role of HCMV-specific decidual-tissue-resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.

A Change in ECM Composition Affects Sensory Organ Mechanics and Function.

Proprioception requires the transduction of muscle-generated deformations into sensory neuronal impulses. In proprioceptive organs, the mechanical coupling between the sensory neuron and the muscle is mediated by a connective structure composed of accessory cells and an extracellular matrix (ECM). Here, we use the fly chordotonal organ (ChO) to investigate how the mechanical properties of the connective element affect mechanosensing. We show that the loss of Pericardin, a major constituent of the ChO ECM, alters the mechanical properties of the ChO resulting in short-wavelength buckling of the accessory cells upon muscle contraction and low compressive strain within the organ. We explain these results using a simplified theoretical model of an elastic beam interacting with an elastic network under a compressive force. We further demonstrate that the transition from compression to bending interferes with the ability of the accessory cells to propagate muscle-generated deformations correctly to the neuron and hence with proper sensing.

Loss of thrombospondin reveals a possible role for the extracellular matrix in chordotonal cap cell elongation.

In the Drosophila larva, major proprioceptive input is provided to the brain by sub-epidermal stretch receptors called chordotonal organs (ChO). Similarly to the body wall muscle that needs to be attached on both of its sides to the larval exoskeleton in order to generate movement, the sensory unit of a ChO must be stably anchored to the cuticle on both of its sides in order to sense the relative displacement of body parts. Through an RNAi screen we have identified thrombospondin (Tsp), a secreted calcium binding glycoprotein, as a critical component in the anchoring of ChOs to the cuticle. We show that the Tsp protein starts to accumulate in the extracellular matrix (ECM) surrounding the ChO attachment cells towards the end of embryogenesis and that it becomes highly concentrated at the attachment junction during larval stages. In the absence of Tsp, the ChO's accessory cells fail to form a stable junction with their epidermal attachment cells and organ integrity is not maintained. Tsp is a known player in the establishment of the myotendinous junctions in both invertebrates and vertebrates. Thus, our findings extend the known similarities between muscle-attachment and ChO-attachment cells. In addition to its role in establishing the ChO attachment junctions, Tsp was found to affect ligament cell migration and cap cell elongation. Most interestingly, the Tsp protein was found to decorate the ChO cap cells along their entire length, suggesting that the elongated cap cells are supported by the ECM to which they attach via integrin-based, Tsp-dependent, adhesion plaques. The ECM enwrapping the cap cells is probably important for keeping the cap cells fasciculate and may also provide mechanical support that allows the extremely elongated cells to maintain tension.