61 research outputs found
Strain-Dependent Migration of CD4 and CD8 Lymphocyte Subsets to Lymph Nodes in NOD (Nonobese Diabetic) and Control Mice
Subpopulations of lymphoid cells were compared with respect to their ability to migrate into
peripheral lymphoid organs of nonobese diabetic (NOD) mice and various strains of control
mice. In short-term, in vivo homing studies, no major differences in the pattern of homing
of B and T cells were observed among all mouse strains studied. On the other hand, CD4
cells localized consistently more efficiently than CD8 cells in both PP and LN of adult NOD
and BALB/c mice, whereas both populations migrated roughly equivalently in LN of adult
DBA/2, CBA, and C57BL/6 mice. No age-dependent differences in the homing of CD4 and
CD8 cells were observed in BALB/c mice. On the contrary, in 2-week-old NOD mice, CD4
and CD8 cells migrated equally well. The preferential entry of CD4 cells in adult NOD and
BALB/c did not result from increased blood transit time of CD8 cells. On the other hand,
the preferential migration of CD8 cells was observed in the liver, whereas the two T-cell
subsets migrated equally well in the lungs. The differences in the homing characteristics of
CD4 and CD8 cells among NOD, BALB/c, and C57BL/6 mice were not related to
modifications in the level of expression of adhesion molecules such as MEL-14, LFA-1, and
Pgp-1
Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia
Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibioticâsusceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria
Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production
Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection
Spleen-Resident CD4+ and CD4â CD8αâ Dendritic Cell Subsets Differ in Their Ability to Prime Invariant Natural Killer T Lymphocytes
One important function of conventional dendritic cells (cDC) is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8α+ and CD8αâ cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4â and CD4+ CD8αâ cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4â and CD4+ cDC are equivalent in their capacity to prime and direct CD4+ and CD8+ T cell differentiation. In contrast, in response to α-galactosylceramide (α-GalCer), CD4â and CD4+ cDC differentially activate invariant Natural Killer T (iNKT) cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up α-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4+ counterparts, CD4â cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12) by cDC. Our data reveal a novel functional difference between splenic CD4+ and CD4â cDC subsets that may be important in immune responses
Enhancement of Adjuvant Functions of Natural Killer T Cells Using Nanovector Delivery Systems: Application in Anticancer Immune Therapy
Type I natural killer T (NKT) cells have gained considerable interest in anticancer immune therapy over the last decade. This âinnate-likeâ T lymphocyte subset has the unique ability to recognize foreign and self-derived glycolipid antigens in association with the CD1d molecule expressed by antigen-presenting cells. An important property of these cells is to bridge innate and acquired immune responses. The adjuvant function of NKT cells might be exploited in the clinics. In this review, we discuss the approaches currently being used to target NKT cells for cancer therapy. In particular, we highlight ongoing strategies utilizing NKT cell-based nanovaccines to optimize immune therapy
Adhesion molecules used by T lymphoblasts to interact with cultured high endothelial cells [Abstract]
Role of the D Prostanoid Receptor 1 in the Modulation of Immune and Inflammatory Responses
Adhesion molecules used by T lymphoblasts to interact with cultured high endothelial cells
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