scholarly journals Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

2021 ◽  
Vol 9 (6) ◽  
pp. 1317
Author(s):  
Matteo Bulati ◽  
Rosalia Busà ◽  
Claudia Carcione ◽  
Gioacchin Iannolo ◽  
Giuseppina Di Mento ◽  
...  

Currently, Klebsiella pneumoniae is a pathogen of clinical relevance due to its plastic ability of acquiring resistance genes to multiple antibiotics. During K. pneumoniae infections, lipopolysaccharides (LPS) play an ambiguous role as they both activate immune responses but can also play a role in immune evasion. The LPS O2a and LPS O2afg serotypes are prevalent in most multidrug resistant K. pneumoniae strains. Thus, we sought to understand if those two particular LPS serotypes were involved in a mechanism of immune evasion. We have extracted LPS (serotypes O1, O2a and O2afg) from K. pneumoniae strains and, using human monocytes ex vivo, we assessed the ability of those LPS antigens to induce the production of pro-inflammatory cytokines and chemokines. We observed that, when human monocytes are incubated with LPS serotypes O1, O2a or O2afg strains, O2afg and, to a lesser extent, O2a but not O1 failed to elicit the production of pro-inflammatory cytokines and chemokines, which suggests a role in immune evasion. Our preliminary data also shows that nuclear translocation of NF-κB, a process which regulates an immune response against infections, occurs in monocytes incubated with LPS O1 and, to a smaller extent, with LPS O2a, but not with the LPS serotype O2afg. Our results indicate that multidrug resistant K. pneumoniae expressing LPS O2afg serotypes avoid an initial inflammatory immune response and, consequently, are able to systematically spread inside the host unharmed, which results in the several pathologies associated with this bacterium.

2018 ◽  
Vol 8 (1) ◽  
pp. 194-201
Author(s):  
KM. Terlikowska ◽  
MA. Strzyż-Skalij ◽  
K. Kryński ◽  
M. Osmólska ◽  
Z. Łada ◽  
...  

Ovarian cancer is the most threatening cause of death among gynecologic malignancies and represents the fifth leading cause of death from all cancers for women. Research reveals that ovarian cancer patients exhibit significant immune responses against the tumor. In this review of the current literature chiefly the interaction of ovarian cancer tumor cells and the immune system is discussed. There is increasingly growing evidence that pro-inflammatory cytokines are involved in intricate complex of mechanisms responsible for tumorigenesis, and delicate balance between pro- and anti-inflammatory cytokines is critical for the antitumor host immune response.


2008 ◽  
Vol 76 (7) ◽  
pp. 3027-3036 ◽  
Author(s):  
Daniel Sinsimer ◽  
Gaelle Huet ◽  
Claudia Manca ◽  
Liana Tsenova ◽  
Mi-Sun Koo ◽  
...  

ABSTRACT Mycobacterium tuberculosis possesses a diversity of potential virulence factors including complex branched lipids such as the phenolic glycolipid PGL-tb. PGL-tb expression by the clinical M. tuberculosis isolate HN878 has been associated with a less efficient Th1 response and increased virulence in mice and rabbits. It has been suggested that the W-Beijing family is the only group of M. tuberculosis strains with an intact pks1-15 gene, required for the synthesis of PGL-tb and capable of producing PGL-tb. We have found that some strains with an intact pks1-15 do not produce PGL-tb while others may produce a variant of PGL-tb. We examined the early host cytokine response to infection with these strains in vitro to better understand the effect of PGL-tb synthesis on immune responses. In addition, we generated a PGL-tb-producing H37Rv in order to determine the effect of PGL-tb production on the host immune response during infection by a strain normally devoid of PGL-tb synthesis. We observed that PGL-tb production by clinical M. tuberculosis isolates affected cytokine production differently depending on the background of the strain. Importantly, while ectopic PGL-tb production by H37Rv suppressed the induction of several pro- and anti-inflammatory cytokines in vitro in human monocytes, it did not lead to increased virulence in infected mice and rabbits. Collectively, our data indicate that, while PGL-tb may play a role in the immunogenicity and/or virulence of M. tuberculosis, it probably acts in concert with other bacterial factors which seem to be dependent on the background of the strain.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroto Nakajima ◽  
Atsushi Miyashita ◽  
Hiroshi Hamamoto ◽  
Kazuhisa Sekimizu

AbstractIn this study, we investigated a new application of bubble-eye goldfish (commercially available strain with large bubble-shaped eye sacs) for immunological studies in fishes utilizing the technical advantage of examining immune cells in the eye sac fluid ex vivo without sacrificing animals. As known in many aquatic species, the common goldfish strain showed an increased infection sensitivity at elevated temperature, which we demonstrate may be due to an immune impairment using the bubble-eye goldfish model. Injection of heat-killed bacterial cells into the eye sac resulted in an inflammatory symptom (surface reddening) and increased gene expression of pro-inflammatory cytokines observed in vivo, and elevated rearing temperature suppressed the induction of pro-inflammatory gene expressions. We further conducted ex vivo experiments using the immune cells harvested from the eye sac and found that the induced expression of pro-inflammatory cytokines was suppressed when we increased the temperature of ex vivo culture, suggesting that the temperature response of the eye-sac immune cells is a cell autonomous function. These results indicate that the bubble-eye goldfish is a suitable model for ex vivo investigation of fish immune cells and that the temperature-induced infection susceptibility in the goldfish may be due to functional impairments of immune cells.


2017 ◽  
Vol 152 (5) ◽  
pp. S328
Author(s):  
Francesco Covotta ◽  
Andrea Cossu ◽  
Danilo Badiali ◽  
Ivano Biviano ◽  
Adriana Marcheggiano ◽  
...  

Author(s):  
Anita Aminoshariae ◽  
Mohammed Bakkar ◽  
Tracey Bonfield ◽  
Santosh Ghosh ◽  
Thomas A Montagnese ◽  
...  

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.


1970 ◽  
Vol 42 (2) ◽  
pp. 142-146
Author(s):  
EC Okocha ◽  
NC Ibeh ◽  
EO Ukaejiofor ◽  
JC Ebenebe ◽  
JC Aneke ◽  
...  

Background and Objective: In P. falciparum malaria (PFM) infestation there are marked changes in cytokine production as the body mounts an immune response to it. Hence we set out to study these changes.Methods: A total of 158 cases of PFM among children attending the paediatric unit of our hospital and 56 healthy controls were studied. Children with febrile illness were screened for malaria using 10% Giemsa stained blood smear. Patients with positive smears were recruited; co-infected patients – those infected by another organism in addition to plasmodium specie.- were excluded. Whole blood was collected, some into plain tubes for serum cytokine testing and some into EDTA bottles for complete blood count and parasite density (PD) determination. Controls with asymptomatic parasitaemia were excluded.Results: Using the World Health Organization criteria for defining severe malaria; we identified 15 cases of severe and 143 cases of uncomplicated PFM. Significantly elevated levels of interleukin-1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were seen in the uncomplicated and severe forms of PFM. It was observed that the elevated cytokine values correlated with PD (in uncomplicated PFM but not in the severe forms). The difference between PD/absolute monocyte count (AMC) ratio was not significant (p=0.13); while PD/platelet count (PC) and PC/ AMC ratios were significant (p=0.01, and 0.03 respectively) when compared between uncomplicated and severe disease.Conclusion: Our data seems to suggest that subjects with an adequate immune response to the parasite density, in terms of pro-inflammatory cytokine levels, presented with uncomplicated disease; while those who have an inadequate response presented with severe disease. The ratios of (PD/PC) and (PC/AMC), in the positive and negative directions respectively, may be predictors of increased disease severity. These observations may have implications for predicting disease outcome and PFM therapy.Key Words: plasmodium falciparum malaria, pro-inflammatory cytokines, Parasite density/Platelet count ratio, Platelet count/Absolute monocyte


2021 ◽  
Author(s):  
Girish Radhakrishnan ◽  
Varadendra Mazumdar ◽  
Kiranmai Joshi ◽  
Binita Roy Nandi ◽  
Swapna Namani ◽  
...  

Brucella species are intracellular bacterial pathogens, causing the world-wide zoonotic disease, brucellosis.  Brucella invade professional and non-professional phagocytic cells, followed by resisting intracellular killing and establishing a replication permissive niche. Brucella also modulate the innate and adaptive immune responses of the host for their chronic persistence. The complex intracellular cycle of Brucella majorly depends on multiple host factors but limited information is available on host and bacterial proteins that play essential role in the invasion, intracellular replication and modulation of host immune responses. By employing an siRNA screening, we identified a role for the host protein, FBXO22 in Brucella -macrophage interaction. FBXO22 is the key element in the SCF E3 ubiquitination complex where it determines the substrate specificity for ubiquitination and degradation of various host proteins.  Downregulation of FBXO22 by siRNA or CRISPR-Cas9 system, resulted diminished uptake of Brucella into macrophages, which was dependent on NF-κB-mediated regulation of phagocytic receptors. FBXO22 expression was upregulated in Brucella -infected macrophages that resulted induction of phagocytic receptors and enhanced production of pro-inflammatory cytokines through NF-κB. Furthermore, we found that FBXO22 recruits the effector proteins of Brucella , including the anti-inflammatory proteins, TcpB and OMP25 for degradation through the SCF complex. We did not observe any role for another F-box containing protein of SCF complex, β-TrCP in Brucella -macrophage interaction. Our findings unravel novel functions of FBXO22 in host-pathogen interaction and its contribution to pathogenesis of infectious diseases.


Reumatismo ◽  
2015 ◽  
Vol 66 (4) ◽  
pp. 277 ◽  
Author(s):  
P. Galozzi ◽  
O. Negm ◽  
E. Greco ◽  
N. Alkhattabi ◽  
A. Gava ◽  
...  

2000 ◽  
Vol 113 (20) ◽  
pp. 3549-3550
Author(s):  
M.J. Townsend ◽  
A.N. McKenzie

The Cytokine Network edited by Fran Balkwill Frontiers in Molecular Biology Series (seried editors B. D. Hames and D. M. Glover) Oxford University Press (2000) pp. 199. ISBN 019–963-702-4. 29.95 Cytokines are small- to medium-sized proteins and glycoproteins that mediate highly potent biological effects on many cell types. They have critical roles in haematopoiesis, inflammatory responses and the development and maintenance of immune responses. Importantly, cytokines act in networks or cascades. Typical properties of cytokines in these networks are pleiotropy, redundancy, synergistic activity and antagonistic effects upon each other. Knowledge of how these networks are comprised and operate is important in understanding how cytokines mediate their diverse effects on biological systems. In The Cytokine Network, Fran Balkwill brings together some distinguished investigators to produce a survey, in eight independently written and concise chapters, of the complex cytokine and chemokine (chemotactic cytokine) networks present in mouse and man. The ever-increasing complexity of cytokine networks is introduced in the initial chapter with a summary of the bioinformatics approach for the high throughput discovery of novel cytokines and chemokines. The burgeoning number of newly identified chemokines, chemokine receptors and TNF family members reminds us that our understanding of the cytokine network is extremely dynamic and that our interpretation of some pathways will change with the characterisation of new factors. The following chapters address the interactions of the cytokines, both with reference to their signalling pathways (well summarised in chapter 2) and their biological roles. The point is made that cytokines should be studied as a network rather than individually and that in vivo models, including the generation of transgenic and gene knock-out mice, are powerful tools for doing so. Rheumatoid arthritis is presented as a well-studied example of how inappropriate regulation of pro- and anti-inflammatory cytokines mediates autoimmune disease, and examples of immunoregulatory cytokines that have both overlapping and independent regulatory effects on inflammation are demonstrated within this context. The important Th1/Th2 paradigm receives a dedicated chapter. T helper type 1 and T helper type 2 cells produce distinct and restricted patterns of cytokines that cross regulate each other and thus mediate different types of immune response. The development of these subsets of T helper cells from a common precursor, as part of a developing immune response, has important effects on the cytokine network. The mechanisms of Th1/Th2 development together with modulating factors and associated intracellular signalling are well described. The chapter summarises well the role of Th1/Th2 development in human diseases with reference to transplantation immunology, neonatal development, autoimmune diseases, and atopic diseases. A very interesting review of the relationships between cytokines and viruses is given. Cytokines are critically involved in mediating antiviral immune responses. However, homologues of cytokines, chemokines and their receptors, after being ‘hijacked’ from the host genome and undergoing evolution along with the viral genes, are utilised by viruses themselves to promote their replication and to suppress immune responses against them. The chapter describes several noteworthy examples of these virally encoded cytokines and receptors together with their roles in vivo. This is a well-written book that provides a good introduction to understanding how cytokines and chemokines interact as a network in the immune system. The volume links together diverse subjects that include cytokine signalling, genomic polymorphism, disease processes and immunotherapies. The book does not aim to describe comprehensively the biology of all the currently known cytokines and chemokines and therefore alternative texts should be considered for this. (ABSTRACT TRUNCATED)


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