Biomedical subjects
Publications and source records attributed to M Galdiero.
Many studies shown that the capacity of the bacteria to adhere to the host cells is a fundamental requisite to the onset of any colonization process and hence infection. Our results shown that E. coli strains from patients with recurring urinary tract infections showed a high degree of surface hydrophobicity, correlated with the presence of numerous fimbriae with respect to a control group.
In our present study we have examined the phagocytosis by polynucleates towards bacteria exposed to macrophages or lymphocytes. Our results show that for almost all the bacterial strains, the contact with lymphocytes determines changes in hydrophobicity correlated to variations in the possibility of being phagocytized and of more significant intracellular killing with respect to bacteria treated with macrophages.
We have verified the consequences of alterations of the lipidic phase of HEp 2 cell membranes on susceptibility to infection from Herpes simplex virus, and have related these results to modification in membrane fluidity. This was carried out by treating HEp 2 cells with saturated and unsaturated fatty acids with chain lengths from eight to 18 carbon atoms. The results show that HEp 2 cells treated with saturated fatty acids with eight and ten carbon atoms have both increased membrane fluidity and increased susceptibility to Herpes simplex virus infection while both parameters were reduced when HEp 2 cells were treated with saturated fatty acids having 14 and 18 carbon atoms. Fatty acids with 16 carbon atoms, however, show an increase in membrane fluidity which has no significant correlation to infection susceptibility. As to unsaturated acids, those with eight carbon atoms, 2-octenoic acid (trans-8: 1[2]) and 2-octynoic acid (8:::1[2]), increase the susceptibility to infection and fluidity while low concentrations of monounsaturated acids with 14 and 18 carbon atoms, myristoleic acid (cis-14:1[9]) and oleic acid (cis-18:1[9]), reduce both the susceptibility to infection and the fluidity of the membrane.
The continuous stimulation of the immune system using cell wall antigens from Brucella melitensis was found to cause both quantitative and qualitative changes in circulating lymphocyte populations in mice. Animals were inoculated in the hind legs with antigens on alternate days for varying lengths of time. During a two-month period, we saw a higher number of circulating lymphocytes, with an increase in the number of CD4+ cells (L3T4+) and B lymphocytes (I-Ad). After two months, a drop in the overall number of circulating lymphocytes occurred, with a decrease in CD4+ cells and an increase in CD8+ cells. During the first two months, we observed a size increase in popliteal lymph nodes and an elevated humoral response. The response then waned with the declining CD4+ cells. In the first two months, the treated animals also showed an in vitro response to two mitogens, concanavalin A and lipopolysaccharide and to the cell wall fraction, after which the treated animals showed a decreased response.
We investigated the association and the invasion of a bovine aortic endothelial cell (BAEC) line by Pasteurella multocida to study the potential role of internalized bacteria and possible intracellular survival during Pasteurella infections. Our data indicate that P. multocida is able to adhere to and to invade BAECs. The density of the bacterial population plays a defined role for an optimal mechanism of interaction between bacteria and cells, as does the incubation period of association and invasion. The optimal bacteria/cells ratio was found to be 100/1, while the optimal infection time was approximately 4 h of incubation. Bacterial internalization was dependent on microfilament and microtubule stability. The invasion ability of P. multocida in the presence of cytochalasin D was reduced by 60%; in the presence of colchicine it was reduced by 97% and in the presence of nocodazole it was reduced by 95%. Our data show that internalized P. multocida did not induce mortality of invaded endothelial cells. Some Pasteurella cells were able to survive and undergo exocytosis.
The aim of this study was to evaluate the effect of the Heat Shock Proteins GroES, GroEL and DnaK on the expression of the costimulatory molecules CD80/CD86 in B cells and macrophages. The interactions among these molecules are able to highly influence the immune response through the regulation of cytokine liberation which, on their own, are able to regulate the immunological response by a feedback mechanism. Our results showed that, on B cells, GroES and GroEL stimulated the expression of CD86 but did not induce the increase of the CD80 expression. CD86 peak expression showed a peak after 24-48 h of culture and decreased 60h after the stimulation. GroES and GroEL also stimulated the expression of CD80 and CD86 on macrophages. The same HSPs did not modify the expression of CD80 and CD86 on cells having characteristics of activated macrophages, the A-THP-1 cell line. DnaK did not induce any increase in the expression of CD80 and CD86 on lymphocytes or macrophages.
Prolactin (PRL) is a pituitary hormone and a cytokine known to regulate several physiological functions. It plays a role in modulating the immune system of rodents and humans. A hormonal protection against listeria and salmonella infections has been previously ascribed to effects of PRL on immunocompetent cells. Here, the role of PRL in the Th1-Th2 response was evaluated based on the pattern of cytokines release by splenocytes from hyperprolactinemic mice infected with Salmonella enterica serovar Typhimurium. Hyperprolactinemia by pituitary graft reduced the number of bacteria in spleens of in vivo infected mice. Modulation of Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-10) cytokine production by splenic cells was found. Our results indicate that PRL can up-regulate IFN-c and IL-12 secretion in response to salmonella infection, confirming its in vivo immunostimulatory effect and suggesting hormonal participation in the genesis and sustenance of the Th1 response.
We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in atherosclerotic carotid plaques and PBMC from the same patients; (iii) the correlation between circulating anti-chlamydial antibodies and the presence of C. pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC specimens from patients with asymptomatic carotid atherosclerosis were examined by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C. pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS). With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of atherosclerotic carotid plaques and in 44.4% of PBMC specimens(P=0.05). In 18 patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic carotid plaques coincided (P=0.005). No statistically significant association was found between anti-C. pneumoniae antibodies (IgG and IgA) and positive PCR results. In conclusion, our results suggest that the detection of C. pneumoniae DNA in PBMC specimens seems to be a first-choice method to identify the patients at risk for endovascular chlamydial infection.
Studies were carried out on the ability of protein A (PA) and of muramic acid (MA) from S. aureus to induce the release of cytokines both from monocytes and lymphocytes in vitro. Results show that protein A induces the greatest activity, compared to the activity already known for the theicoic acid (TA) and for muramyl dipeptide (MDP). At concentration of 10 micrograms/ml; PA induces roughly +180% release of TNF with respect to controls, while release of IL-1 alpha is about 500% control values, and is higher than those obtained when cells are treated with TA and MDP; IL-6 release is higher than that stimulated by Con A, used as standard challenge. At PA concentrations of 5 micrograms/ml, IL-4 release is about five times higher than that induced by Con A. Release of IFN-gamma showed similar dose-dependent stimulations. Muramic acid (MA) is particularly active in inducing the release of cytokines from target cells, inducing TNF release of about +75% with respect to the controls. This increase is less than that obtained with PA. Also IL-4 and IFN-gamma are released by PA in quantities higher than those induced by TA and MDP. Our results lead us to believe that during infections by Gram-positive bacteria, their surface components are able to induce a series of chain reactions ranging from the inflammatory to the immunologic responses which are also conditioned by release of cytokines.
The regulation by peptide hormones (Growth Hormone, Prolactin, Insulin) of cytokine secretion by splenocytes stimulated with Staphylococcal Enterotoxin A was studied. Growth hormone increases the release of IFN-gamma from splenocytes stimulated with Enterotoxin A by 50% but considerably decreases IL-1 alpha release by 93%. Prolactin decreases the release of IL-1 alpha by 80%, but has no significant effects on IFN-gamma release. Insulin causes a 50% decrease in IFN-gamma and 95% decrease in IL-1 alpha. IL-4 release was not changed. The results are discussed in terms of the possibility of an interesting function for these endocrine peptides which expands their range of biologic activities within the immune system.