NK cells are lymphocytes of the innate immune system which are a first line of defense against infections and tumor cells, in bone marrow and peripheral organs like lung and spleen. The lung is an organ in contact with respiratory pathogens and the site of inflammatory disorders triggered by the respiratory environment. In contrast, spleen is a lymphatic organ connected to the blood system which regulates the systemic immune response. Here we compare NK cell maturation and expansion as well as expression of NK cell receptors in spleen and lung compartments. We show that spleen and lung NK cells differ in phenotypic and functional characteristics due to a difference of maturity and cellular microenvironment. Indeed we observe that spleen and lung macrophages have the capacity to influence the cytotoxicity of NK cells by cell-to-cell contact. This suggests that the differences of NK cell subsets are in part due to a modulation by the organ environment.

Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN−/− mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN−/− dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN−/− mice had significantly increased markers of airway remodeling like collagen deposition. NTN−/− lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models.

The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) and interferon-y (IFN-y) on the resistance against Listeria monocytogenes infection in mice was investigated. It was shown that administration of MTPPE or IFN-y at 24 h before bacterial inoculation led to increased resistance against L. monocytogenes infection in terms of a decrease in bacterial numbers in liver and spleen. Encapsulation of MTPPE and IFN-y in liposomes increased their efficacy 33- or 66-fold, respectively. In addition, liposomal encapsulation led to a more rapid decrease in bacterial numbers. The immunomodulator to lipid ratio appeared to be very important in the antibacterial effect of LE-MTPPE and LE-IFN-y. When nontherapeutic doses of liposome-encapsulated MTPPE or IFN-y were administered in a larger amount of lipid (so at higher lipid: immunomodulator ratio), these doses became effective. Exposure of macrophages in monolayer infected with L. monocytogenes in vitro to MTPPE had no effect, whereas exposure to IFN-y only led to growth inhibition of the intracellular bacteria. However, incubation of macrophages with a combination of MTPPE and IFN-y resulted in killing of the intracellular bacteria. Exposure of macrophages in vivo to both immunomodulators in combination can be effected by using liposomes as carriers. It was observed that administration of MTPPE and IFN-y co-encapsulated in liposomes resulted in a synergistic enhanced antibacterial resistance against L. monocytogenes. Both reactive oxygen and nitrogen intermediates seemed to play a role in the killing of L. monocytogenes by macrophages activated with a combination of MTPPE and IFN-y.

NK cells are lymphocytes of the innate immune system which are a first line of defense against infections and tumor cells, in bone marrow and peripheral organs like lung and spleen. The lung is an organ in contact with respiratory pathogens and the site of inflammatory disorders triggered by the respiratory environment. In contrast, spleen is a lymphatic organ connected to the blood system which regulates the systemic immune response. Here we compare NK cell maturation and expansion as well as expression of NK cell receptors in spleen and lung compartments. We show that spleen and lung NK cells differ in phenotypic and functional characteristics due to a difference of maturity and cellular microenvironment. Indeed we observe that spleen and lung macrophages have the capacity to influence the cytotoxicity of NK cells by cell-tocell contact. This suggests that the differences of NK cell subsets are in part due to a modulation by the organ environment.