In vitro experiments have revealed that DMF, as well as its primary metabolite monomethyl fumarate (MMF), can exert immunomodulatory effects on T-cell subsets as well as on antigen-presenting cells,[93, 94] and experiments in EAE have demonstrated that DMF is effective in

both preventive MK0683 and therapeutic applications, albeit marginal in chronic EAE, promoting myelin and axonal preservation and reducing astrocyte activation.[95, 96] It has been speculated that part of the effect of DMF could be mediated through modulation of microglia phenotype. Histological studies demonstrated that, during the acute phase of EAE, Mac-3-positive cells (microglia and macrophages) are significantly reduced in the spinal cord of DMF-treated animals.[95] Such an observation is also supported by in vitro studies in which pre-treatment with DMF can inhibit LPS-induced activation of microglial cells by reducing

the expression of NO, TNF-α, IL-1β and IL-6, possibly through an inhibition of the extracellular-signal regulated kinase pathway and an activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.[97] While in vitro data prompted the hypothesis that DMF and MMF could affect microglia activation through Nrf2, Ku-0059436 clinical trial a pathway involved in the expression of proteins critical in the detoxification of reactive oxygen and reactive nitrogen species,[97, 98] this has not been demonstrated in vivo. Indeed, although Linker et al.[96] showed

that Nrf2 is required for the therapeutic effect of DMF, double-labelling Casein kinase 1 of Nrf2 with a marker for microglia did not reveal an increase of its expression in those cells after DMF treatment in EAE-affected mice. Further in vitro and in vivo studies are needed to dissect the pathways through which DMF promote an alternative neuroprotective phenotype in microglia. Mesenchymal stem cells (MSC) are currently being investigated as an alternative therapeutic approach for MS.[99] The potential therapeutic use of MSC for neurodegenerative diseases was originally considered as related to their possible regenerative function through their ability to differentiate into mesodermal tissues and perhaps into other embryonic lineages. However, recent observations have indicated that, upon systemic administration, most MSC are rapidly entrapped in the lungs, and only a few engraft into injured CNS, where they display negligible transdifferentiation capacity.[100-102] In vitro studies demonstrating that MSC can modulate several effector functions of cells of both the adaptive and innate immune systems introduced the possibility that MSC might be effective in EAE. Indeed, Zappia et al.

This is illustrated in infection with Chlamydia trachomatis, Salmonella Typhimurium, Francisella selleck chemicals tularensis, Mycobacterium tuberculosis, and Leishmania major. In the case of Chlamydia infection, B-cell-deficient and FcγR-deficient mice not only have a significantly higher mortality rate than wild-type mice in lethal challenges but also show reduced Th1 responses and fail to mount an efficient DTH response 37–39. Analogous observations have been made when protection against S. Typhimurium was studied. As seen in Chlamydia infection, B-cell-deficient mice are not protected against lethal challenge with Salmonella and develop reduced Th-cell responses marked by lower levels

of IFN-γ and IL-2 40, 41. In addition, when Ab-opsonized Salmonella are added to DCs in vitro, the DCs process and present Ag more efficiently than in the absence of Abs and

are able to stimulate enhanced T-cell activation 42, 43. The interaction of Abs with activating www.selleckchem.com/products/Erlotinib-Hydrochloride.html FcγRs is also required for optimal protection in M. tuberculosis-infected mice, as aerogenically infected μMT mice, as well as FcRγ−/− mice, show exacerbated immunopathology corresponding with elevated pulmonary recruitment of neutrophils and increased levels of IL-10 in the lung 44, 45. On the contrary, mice lacking inhibitory FcγRIIB manifest enhanced mycobacterial control upon infection and have increased Chorioepithelioma levels of Th1-promoting IL-12 45. Similarly, the protective effect of passively transferred Abs against Francisella has been attributed to limited sequelae associated with infection and an increased T-cell response in the presence of Abs 46, 47. Protective

effects of Ab–FcR interactions on T-cell responses have also been described for infections with intracellular parasites as described in the next section. In the absence of specific Abs, L. major amastigotes are phagocytosed by macrophages, which present Ag on MHC class II and activate memory, but not naïve, T cells; however, when L. major-specific IgG is present, amastigotes are taken up by DCs via FcγRI and II, which results in DC activation and production of IL-12 by the DCs. In contrast to macrophages, DCs are able to effectively prime naïve T cells and the resulting Th1 response leads to smaller lesions and reduced parasite burden 48. On the contrary, the presence of Abs during Leishmania mexicana infection drives a Th2 response and leads to the development of chronic lesions, whereas FcRγ−/− mice are resistant and able to resolve lesions by mounting a Th1 response. Resistance to L. mexicana is also observed in FcγRIII−/− mice, indicating that this receptor is responsible for shifting T-cell responses toward a Th2 phenotype via IL-10 production by macrophages 49, 50.

Translated clinically, this suggests that patients suffering from autoimmune diseases may develop steroid resistance due to persistent CORT exposure; in the absence of careful control over steroid resistance measures,

Ensartinib purchase patients may thereby enter a vicious cycle where they become dependent on increasing doses of steroids. Eight-week-old C57BL/6 mice were purchased from Harlan (Jerusalem, Israel) and were allowed to acclimatize to our animal facility for 7 days prior to the experimental period. All mice were housed under standard environmental conditions (12:12 light:dark cycle with light onset at 7:00 a.m.) and were allowed free access to food and water throughout the experimental period. Surgical and experimental procedures were approved by the Institutional Animal Care PXD101 cell line and Use Committee (IACUC) of Ben-Gurion University of the Negev, Israel. To detect intracellular FoxP3 we used C57BL/6 transgenic mice expressing enhanced green florescent protein under the control of the mouse FoxP3 promoter. The mice were kindly provided by Dr. Eli Lewis. Mice were randomly assigned into two groups: (i) a group of isolated mice exposed to CVS for 24 days as described below, (ii) and a group of nonstressed mice, kept in groups of 4–8 mice per cage and manipulated only once a week for urine collection and body weight measurement. Following the 24-day experimental period,

mice in the stressed and nonstressed groups were further divided into three groups: (i) mice subjected to behavioral tests, after which they were killed for immunological analysis; (ii) mice injected with MOG35-55 emulsified second in CFA to induce EAE as described below; and (iii) mice injected with the CORT antagonist mifepristone (Sigma, Israel) daily, 2 hours before exposure to the stressful conditions, throughout the stress period. Mifepristone was dissolved in 100% ethanol and diluted to 5% ethanol in corn oil to a final concentration of 3 mg/mL. A daily dose of 30 mg/kg was injected subcutaneously. Chronic unpredictable stress paradigms typically

follow a schedule of repeated exposure to several randomly assigned stressors a day. The CVS procedure was developed based on several paradigms previously validated as stress inducers in rodents. These included isolation [55]; exposure to cat urine [56]; restraint (placing the mouse in a well-ventilated 50 mL polypropylene tube, 2.8 cm in diameter and 11.5 cm in length) [57]; swimming in cold (4°C) water [58]; illumination during the dark phase, and tilting the home cage at a 45o inclination for 24 hours [30]. Stressor types and stress durations throughout the experiment are provided in Table 1. Stressed and nonstressed mice were tested to evaluate anxiety-like behaviors 24 hours after termination of the experimental protocol (i.e. on day 25) using the following behavioral tests.

Streptococcus salivarius DSM 23307, characterized in this study, is sensitive to the main antibiotics used for the treatment of URTIs, does not possess dangerous enzymatic reactions, as demonstrated by its metabolic profile, and lacks the main streptococcal virulence genes, that is, sagA, smeZ-2, and speB. All this is further proof of its virtuous nature. Moreover, a fundamental property of this strain is its strong BLIS activity against S. pneumoniae including virulent and multidrug resistance strains such as the most diffused serotypes circulating in our country

involved in severe infections in children and adults (Resti et al., 2010; Ansaldi et al., 2011); furthermore, it does not interfere with other S. salivarius strains. The BLIS activity of S. salivarius DSM 23307

is not associated with typical streptococcal bacteriocin genes such as salA, sboB, srtA, scnA, and sivA as demonstrated by PCR experiments, selleck compound suggesting the presence of variant or different antimicrobial peptide genes. These molecular data correlated with its unusual inhibitory spectrum primarily oriented SB203580 ic50 versus S. pneumoniae and only in particular growth conditions, that is, in TSYCa versus S. pyogenes. The strong in vitro capacity to inhibit S. pneumoniae resembles the BLIS activity of the nisin inhibitory spectrum (Goldstein et al., 1998), even if the Clomifene presence of this gene was excluded. Another essential characteristic of strains for use as bacterial replacement therapy is their capability to adhere to host tissues: the cells of S. salivarius DSM 23307 remained attached to the HEp-2 monolayer demonstrating a good adherence capacity. In conclusion, in this study, we identified one strain as a potential oral probiotic, possessing desirable characteristics for bacteria-therapy: S. salivarius DSM 23307 possesses a strong activity against S. pneumoniae and is harmless to other S. salivarius strains, it is non-pathogenic for the host as demonstrated by safety assessment and

it efficiently adheres to human larynx cells. Further studies on S. salivarius DSM 23307 are ongoing both to completely characterize the antimicrobial peptides and to confirm its probiotic use in humans. This work was supported in part by DMG Italia s.r.l. and by research funding of S.S. and M.S. The authors thank Antony Bridgewood for the language revision. “
“Programmed death-ligand 1 (PD-L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death-1 (PD-1). However, the mechanism of PD-L1-mediated inhibitory signalling after PD-L1 cross-linking by anti-PD-L1 monoclonal antibody (mAb) or PD-1–immunogloblin fusion protein (PD-1-Ig) is still unknown, although it may induce cell death of PD-L1+ cells required for regular immune reactions.

Active EAE is induced by autoantigen immunization, whereas passive EAE is induced by the adoptive transfer of encephalitogenic T cells. Although the NLRP3 inflammasome is activated in both active and passive

EAE,[44] Asc−/− and Nlrp3−/− mice can develop severe EAE if the active EAE induction regimen is aggressive.[44] In active EAE induction, autoantigen emulsified in complete Freund’s adjuvant (CFA) plus injections of pertussis toxin is used. To induce EAE in Asc−/− and Nlrp3−/− mice, increased dosages of heat-killed Mycobacterium tuberculosis (Mtb) in CFA alone are sufficient.[44] A similar observation was reported in a study using Casp1−/− mice, selleck chemicals llc in which disease susceptibility is associated with repeated immunization, and high dosages or high MHC-binding affinity of antigen peptides.[45] These studies suggest the presence of an NLRP3 inflammasome-independent pathway in progression of EAE. In addition, the studies cited herein suggest that dosages of adjuvant and/or the abundance of high-affinity antigen shift EAE to an NLRP3

inflammasome-independent disease. Two earlier reports on NLRP3 inflammasome in EAE showed important but contrasting results. Aloxistatin clinical trial One showed susceptibility of Nlrp3−/− mice to EAE,[78] while the other showed resistance of Nlrp3−/− mice.[41] As a result, the requirement of NLRP3 inflammasome in EAE was considered to be controversial, wherein the “basis for these conflicting data” was said to be unknown.[79] Here, we assume that the two distinct results reflect two different subtypes of EAE: NLRP3 inflammasome-dependent and -independent. The EAE induced in Asc−/− and Nlrp3−/− mice are clearly NLRP3 inflammasome-independent. Astemizole However, in wild-type mice, two subtypes of EAE, NLRP3 inflammasome-dependent

and -independent, may be occasionally occurring at the same time, particularly when disease induction is not aggressive enough. In other words, the two subtypes are not mutually exclusive during EAE development. Depending on the triggers of the disease, and the genetic environment at hand, it is possible that the balance between the two subtypes may be altered. We have therefore shown that aggressive immunization induces NLRP3 inflammasome-independent EAE.[44] We must then ask: What is the equivalent to such NLRP3 inflammasome-independent EAE in human disease? If there is NLRP3 inflammasome-independent MS, it might be caused by intensive stimulation on innate immune cells, or by other factors that provide strong autoantigen affinity to T cells. This, we believe, is an important and intriguing possibility. Although IFN-β is a first-line drug to treat MS, it has been found that one-third of patients do not respond to IFN-β treatment.[80] Is IFN-β still effective without activated NLRP3 inflammasome, which is a target of IFN-β? This question was addressed in NLRP3 inflammasome-independent EAE.[44] Results suggest that IFN-β was not effective in treating EAE in Asc−/− and Nlrp3−/− mice.

It is caused by the dimorphic fungus Paracoccidioides brasiliensis, which affects, among other organs in the human body, the oral cavity. Fungus virulence and immunocompetence of the host determine the establishment of infection or active disease, whose severity and clinical behaviour depend mostly on the cellular immune response of the host. Often, oral lesions constitute the first sign and site of confirmation of diagnosis, which in most cases is delayed. The success of the treatment depends on early and correct diagnosis, as well as on the patient’s adherence to the drug therapy. “
“Regulation of morphogenesis Trametinib manufacturer through the production

of chemical signalling molecules such as isoamyl alcohol, 2-phenylethyl alcohol, 1-dodecanol, E-nerolidol and farnesol is reported in Candida albicans. The present study focuses on the effect of ethyl alcohol on C. albicans dimorphism and biofilm development.

Ethyl alcohol inhibited germ tube formation induced by the four standard inducers in a concentration-dependent manner. The germ tube inhibitory concentration (4%) did not have any effect on the growth and viability of C. albicans cells. Ethyl alcohol also inhibited the elongation of germ tubes. Four percentage of ethyl alcohol significantly inhibited biofilm development on MAPK Inhibitor Library ic50 polystyrene and silicone surfaces. We suggest a potential morphogenetic regulatory role for ethyl alcohol, which may influence dissemination, virulence and establishment of infection. “
“Heat shock proteins (Hsp) are highly conserved molecules, which are both constitutively expressed and up-regulated

in response to various stress conditions. In particular, fungal Hsp60 can act as immunodominant antigens and facilitate powerful immunological properties. A possible cellular heat shock response was investigated in eight fungi (Aspergillus fumigatus, Aspergillus terreus, Penicillium chrysogenum, Cladosporium cladosporioides, Scedosporium apiospermum, Trichophyton mentagrophytes, Candida albicans and Saccharomyces cerevisiae). Fully automated RNA extraction was followed by quantitative real-time RT-PCR targeting fungus-specific Hsp60 mRNA and sequencing of the amplicon. Levels Avelestat (AZD9668) of temperature-dependent gene expression were evaluated and rates of similarity and identity were compared. While Hsp60 mRNA was constitutively expressed in all the samples tested, a temperature-dependent induction was not shown in C. cladosporioides. In the 80-amino acid fragment from the hypothetical protein, 66% of the amino acids were identical, 20% showed a conserved and 8% a semi-conserved substitution. Our findings should contribute to a better understanding of host–pathogen relationship and suggest that fungal Hsp60 under temperature-related stress conditions might act as an immunogenic trigger in orchestrating fungi-related diseases. “
“Dermatomycoses are very common worldwide with increasing prevalence.

0 GeneChip (Affymetrix) as described by the manufacturer. Washing and staining steps were performed in a Fluidics Station 400 (Affymetrix) according to the technical manual. Microarrays were scanned with the Affymetrix GeneChip Scanner 3000. Signals, detection calls and corresponding p-values of microarrays were calculated with MAS5.0/GCOS algorithms (default mode). Global normalization was used by scaling

the microarrays to a target intensity value of 100. Signal detection of probe sets and scaling factor for the individual microarrays, also correlation coefficients of signal intensities between duplicate microarrays permitted a comparison of the different data sets obtained for FDC networks (primary, early and late secondary FDC n=6), B cells (naïve, early and late GC B cells n=6) and BP3hi reticular cells (n=2) (Supporting Information Table 1) 44. To determine those genes which are specifically expressed in FDC Lumacaftor purchase an in silico subtraction approach was used. Recently, a similar approach was used to analyze the gene expression of the thymic stromal microenvironments https://www.selleckchem.com/products/Adriamycin.html 45. Data sets obtained from dissected FDC networks were compared with those of sorted B cells. Parameters (signal log ratios, change calls and change p-values) provided by the algorithm for pair wise array comparison in the GCOS software

were obtained and group comparisons performed between the two groups of arrays using the High Performance Chip Data Analysis 24. In brief, the different parameters derived from signal calculation by the GCOS software were used to calculate mean, median and standard deviation of signal values and the percentage of “present” calls for each group. The mean of the Signal Log Ratio values and the percentage of change calls were used for pair wise comparison information of all possible comparisons. Finally, different Welch t-tests were performed and only p-values<0.05 were considered to be significant. Microarrays of BP3hi Selleck Baf-A1 reticular cells were analyzed as described above for FDC-specific genes (Fig. 1A, subtraction of B-cell transcriptome) and gene expression

compared with that of primary FDC using a modification of the High-Performance Chip Data Analysis. Hereby, duplicate microarrays of primary FDC and BP3hi reticular cells were compared (altogether four comparisons). On average, the signal intensities on FDC microarrays were 2.6-fold lower than on BP3hi microarrays. Only for those genes with >1.5- or<-1.5-fold differences from the mean value of 2.6 (Fig. 3) in at least three of the four comparisons were considered as significantly different. Gene expression profiles of macrophages (GSM106426, GSM106427, GSM106428, GSM117560, GSM117561), T cells (GSM44979, GSM44980, GSM44981, GSM44982), fibroblasts (GSM106139, GSM106141) and myoblasts (GSM126586, GSM126587) were obtained from the NCBI GEO data base.

Also, the strong homeostatic proliferation that rapidly replenishes the Treg-cell compartment after depletion

of FOXP3+ cells was found to depend on the presence of DCs, in addition to interleukin-2 (IL-2) signaling [25]. Further to their role in Treg-cell homeostasis, steady-state DCs can induce the de novo differentiation of naïve CD4+ T cells into Treg cells in the periphery. These peripherally induced Treg (pTreg) cells [26] are thought to have a nonredundant role in maintaining T-cell tolerance, particularly at environmental interfaces such as skin and mucosal tissues [27]. The induction of pTreg cells by DCs, in vivo as well as in vitro, requires the presence of transforming growth factor β (TGF-β) [28], is greatly enhanced by the vitamin Ponatinib clinical trial A metabolite retinoic acid [29], and is inhibited by the proinflammatory complement fragments C3a and C5a [30]. The capacity to induce pTreg cells seems to be restricted to certain DC subtypes that can produce retinoic acid and reside in peripheral tissues,

such as mucosal CD103+ DCs [29], dermal CD207+DCs [31], and are thus migratory but not lymph node resident DCs [32, 33]. The immature phenotype of steady-state DCs is a prerequisite for tolerance induction via T-cell-intrinsic mechanisms. Upon activation, DCs lose the capacity to delete or anergize autoreactive naïve T cells [14-16]. Similarly, the induction of dominant peripheral tolerance depends Hedgehog antagonist on the DC activation state, although some DC-activating

stimuli might still allow for the DC-dependent induction of pTreg cells. For example, when activated with the TLR3 ligand poly-IC, DCs lose the ability to induce pTreg cells in vitro [34], and DC activation through CD40 ligation prevents pTreg-cell induction by cognate Ag-presenting DCs in vivo [28]. By contrast, DC activation via certain PRRs such as TLR2 has been shown to induce retinoic acid production in DCs, subsequently leading to DC-dependent Exoribonuclease pTreg cell differentiation [35]. However, in general, an immature DC state is essential for induction and maintenance of peripheral tolerance. Facilitated by the development of DC-specific gene targeting, several DC-intrinsic mechanisms have been found to maintain the immature and tolerogenic phenotype of steady-state DCs by downmodulating the signaling pathways that are induced by proinflammatory stimuli. DC-specific deletion of the ubiquitin-editing enzyme A20, which negatively regulates nuclear factor-κβ (NF-κB) signaling, resulted in spontaneous DC activation, expansion of the activated T-cell population and multiorgan autoimmune disease [36]. Mice overexpressing a short splice variant of the ubiquitin-editing enzyme CYLD, which also downregulates the NF-κB pathway, have impaired peripheral tolerance induction, and DCs from these mice display an activated phenotype [37].

We also demonstrate that although TNF-α gene induction was not significantly different in Mal−/− cells when compared with WT cells following poly(I:C) stimulation, a significant decrease in LPS-mediated TNF-α gene induction was evident (Fig. 1B). Next, we sought to investigate the role of Mal in the translational regulation of IFN-β and TNF-α by ELISA. As shown in Fig. 1C, we show that although stimulation of WT BMDM with poly(I:C) resulted in IFN-β induction, a significantly https://www.selleckchem.com/products/PD-0332991.html greater induction of IFN-β was evident in Mal−/− BMDM. Correlating with

real-time PCR data and the previous reports 16–18, LPS and poly(I:C)-induced IFN-β production was significantly decreased in TRIF-deficient BMDM when compared with WT BMDM (Fig. 1C). In accordance with the previous studies showing that Mal P125H and the TIRAP inhibitory peptide block LPS induced IFN-β gene induction 15, 19, we show that LPS-induced IFN-β production was significantly decreased in Mal-deficient BMDM when compared with WT BMDM (Fig. 1C). We also show that TNF-α and IL-6 induction were not significantly different in Mal−/− cells when compared with WT cells following poly(I:C) stimulation (Fig. 1E and F). As expected, click here we demonstrate an impairment of TNF-α and IL-6 induction in Mal- and TRIF-deficient BMDM cells stimulated with LPS

(Fig. 1E and F). To rule out the possibility that enhanced IFN-β in Mal−/− cells may be attributed to the BMDM immortalisation procedure per se, ex vivo BMDM from WT and Mal−/− mice were stimulated with either poly(I:C) or LPS and cytokines were measured by ELISA. Similar to data generated using the immortalised BMDM, poly(I:C)-induced IFN-β production was significantly enhanced in Mal-deficient BMDM when compared with WT BMDM (Fig. 1D). We also show that treatment of BMDM with a Mal inhibitory peptide significantly augmented poly(I:C)-mediated IFN-β gene induction when compared with cells treated with the control-inhibitory

peptide (Fig. 1G). Furthermore, C57BL/6, Mal-deficient and TRIF-deficient BMDM did not exhibit differences in TLR3 mRNA receptor expression, indicating that reported differences in gene induction are not attributable to perturbations in TLR3 Pyruvate dehydrogenase lipoamide kinase isozyme 1 expression levels (Table 1). Contrary to the previous reports 20, the data presented herein demonstrate that poly(I:C)-mediated induction of IFN-β in murine macrophages is TLR3 dependent, as TRIF, the critical adaptor involved in TLR3 signal transduction, is essential for poly(I:C)-mediated IFN-β induction. Also, correlating with the previous reports 21 poly(I:C)-mediated induction of IFN-β, CCL5/Rantes and TNF-α was similar in WT and MAVS−/− BMDM (Supporting Information Fig. 2), suggesting that the TLR and retinoic acid-inducible gene-I-like receptor (RLR) pathways work in parallel to sense viruses.

5a, b). Mice treated with Lr1505 or Lc431 had significantly higher macrophage and neutrophil PI3K inhibitor counts than

did the control group (Fig. 5a, b). We also observed increased concentrations of TNF-α and IFN-γ in the respiratory tract after challenge with pathogenic yeast in all experimental groups (Fig. 5a, b). However, in the groups receiving Lc431 or Lr1505 the concentrations of both cytokines were significantly higher than in the control group (Fig. 5c,d). Several studies have reported beneficial effects of probiotic bacteria and products containing these microorganisms on intestinal health. In the present study, we observed that oral administration of Lc431, Lr1505 and Lr1506 stimulates production of TNF-α and IFN-γ in the intestine. This is in line with other studies showing Maraviroc cost that, of the cytokines induced by immunomodulatory LAB, the most remarkable

effect is the increase in TNF-α, IFN-γ, and the regulatory cytokine IL-10 in all probiotic strains assayed (16). In addition, that TNF-α and IFN-γ are both reportedly produced by antigen presenting cells (17). Therefore, our results indicate that the three lactobacilli strains evaluated in this study are able to stimulate macrophages and dendritic cells in the gut. In addition, we observed a strain-dependent difference in the concentrations of TNF-α and IFN-γ after Lc431, Lr1505 PD184352 (CI-1040) or Lr1506 treatments. This effect has been also observed by other authors who have reported strain-dependent differences in the number of gut TNF-α+

and IFN-γ+ cells after oral administration of Lactobacillus strains (18). Local activation of the gut immune system induced by Lc431, Lr1505 and Lr1506 would explain the improved resistance of treated mice to oral challenge with the intestinal pathogen Salmonella typhimurium (12, 15). We were particularly interested in the effect of lactobacilli strains beyond the intestinal tract. It is known that the gut immune system is anatomically connected to the systemic immune system by the lymphatic and blood circulation. Therefore, immune responses induced in the small intestine can spread through the systemic immune system and reach mucosal and non-mucosal sites (19). Thus, in the present study, we simultaneously studied the effects of oral administration of Lactobacillus strains on sites distant from the gastrointestinal tract by assessing macrophage activity in the peritoneal and alveolar compartments. We found that activation of macrophages at sites distant to the gastrointestinal tract is dependent on the strain of LAB employed. We also demonstrated that the stimulatory effects of the LAB are related to the ability of each strain to influence profiles of mucosal and systemic cytokines. Interaction of macrophages with microorganisms often results in phagocytosis.