scholarly journals Production of Interleukin-12 by Murine Macrophages in Response to Bacterial Peptidoglycan

1998 ◽  
Vol 66 (10) ◽  
pp. 4947-4949 ◽  
Author(s):  
Christine Lawrence ◽  
Charles Nauciel

ABSTRACT Peptidoglycan (PG), a component of the bacterial cell wall, has various immunomodulating activities, including the capacity to induce delayed-type hypersensitivity reactions to antigens administered in Freund’s adjuvant. We report that PG induces interleukin-12 (IL-12) mRNA production and IL-12 secretion by mouse macrophages. The capacity of PG to induce IL-12 production, like its previously reported immunomodulating activities, was dependent on the structure of its peptide subunit. PG from Bacillus megaterium andStaphylococcus aureus induced IL-12 production, whereas PG from Micrococcus luteus and Corynebacterium poinsettiae did not. The ability of most bacterial PGs to induce IL-12 production suggests that they play an important role in triggering host defense mechanisms against bacterial infections.

1997 ◽  
Vol 86 (2) ◽  
pp. 420-427 ◽  
Author(s):  
Chandra Ramamoorthy ◽  
Daniel W. Kovarik ◽  
Robert K. Winn ◽  
John M. Harlan ◽  
Sam R. Sharar

Background Human newborns, particularly those born before full term, are more susceptible to bacterial infections as a result of impaired host defense mechanisms. Compared with adults, circulating leukocytes from human newborns (preterm and full-term gestations) and newborn rabbits (full-term gestation) have low resting levels of CD62L (L-selectin) and do not significantly increase surface expression of CD18 after inflammatory stimulation. To determine the potential utility of preterm rabbits in investigations of perinatal human conditions, the authors compared the surface expression of the beta 2-integrin CD18 and CD62L (L-selectin) on polymorphonuclear leukocytes (PMNs) from perinatal rabbits and perinatal humans, both under resting conditions and after in vitro activation with inflammatory stimulants. Methods After erythrocyte lysis of whole-blood samples, leukocytes from 7-day-old, full-term (31-day gestation), and preterm (24-day gestation) rabbits, as well as full-term (37-42 week gestation) and preterm (27-36 week gestation) human newborns were prepared and stimulated in vitro at 37 degrees C with either C5a or phorbol myristate acetate. After fluorescence labeling of CD18 and CD62L with monoclonal antibodies, PMN adhesion molecule expression was assessed by flow cytometry. Results Constitutive CD18 expression was not significantly different between perinatal and adult humans but was reduced in all perinatal rabbits compared with adults. Inflammatory stimulation caused significant increases in CD18 expression in adult human PMNs but not in full-term and preterm newborns. Changes in CD18 expression in adult and preterm rabbits after stimulation, although in the same direction as humans, were more variable. In both species, constitutive CD62L expression on PMNs from all perinates was significantly lower than in adults. However, CD62L was shed to similar degrees after inflammatory stimulation in all groups. Conclusions Preterm rabbits may provide a potentially useful experimental model to study PMN adhesion and host defense in the perinatal period, particularly preterm gestations. Specific advantages and limitations of rabbits in such studies are discussed.


1963 ◽  
Vol 118 (1) ◽  
pp. 13-26 ◽  
Author(s):  
P. F. Bartell ◽  
I. S. Thind ◽  
T. Orr ◽  
W. S. Blakemore

Staphylococcus bacteriophage 81 is capable of in vivo interaction with Staphylococcus aureus, Type 80/81. This is immediately made evident by increased levels of bacteriophage and concomitant survival of 81 per cent infected mice. The reaction is dependent upon the use of active, type-specific bacteriophage. The maximal protective effect is observed at a bacteriophage to bacteria ratio of 1:2 and decreased quantities of bacteriophage result in decreased protection. Time and sequence of administration are also determining factors. It is evident that bacteriophage administered intravenously is capable of interaction with the infecting bacterial cell at the site of infection. In vivo produced bacteriophage is apparently eliminated or otherwise rendered nondetectable fairly rapidly, occurring within a period of 5 to 10 days. However, it appears that host defense mechanisms are stimulated in the process and actively play a protective role against subsequent challenge inocula administered up to 3 weeks later.


2022 ◽  
Vol 23 (2) ◽  
pp. 948
Author(s):  
Urszula Wójcik-Bojek ◽  
Barbara Różalska ◽  
Beata Sadowska

The main purpose of this review is to present justification for the urgent need to implement specific prophylaxis of invasive Staphylococcus aureus infections. We emphasize the difficulties in achieving this goal due to numerous S. aureus virulence factors important for the process of infection and the remarkable ability of these bacteria to avoid host defense mechanisms. We precede these considerations with a brief overview of the global necessitiy to intensify the use of vaccines against other pathogens as well, particularly in light of an impasse in antibiotic therapy. Finally, we point out global trends in research into modern technologies used in the field of molecular microbiology to develop new vaccines. We focus on the vaccines designed to fight the infections caused by S. aureus, which are often resistant to the majority of available therapeutic options.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lea Weber ◽  
Anna Hagemann ◽  
Jila Kaltenhäuser ◽  
Manuela Besser ◽  
Patrick Rockenfeller ◽  
...  

Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens. However, disruption of IspA, a gene encoding the geranyltranstransferase of Staphylococcus aureus (S. aureus) leads to reprogramming of cellular behavior as well as impaired growth and decreased resistance to cell wall-targeting antibiotics. We used an agar well diffusion assay and a time kill assay and determined the minimum inhibitory concentrations of the FTIs lonafarnib and tipifarnib. Additionally, we conducted cell viability assays. We aimed to characterize the effect of these FTIs on S. aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (S. epidermidis), Escherichia coli (E. coli), Enterococcus faecium (E. faecium), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and Streptococcus pneumoniae (S. pneumoniae). Both the FTIs lonafarnib and tipifarnib were capable of inhibiting the growth of the Gram-positive bacteria S. aureus, MRSA, S. epidermidis, and S. pneumoniae, whereas no effect was observed on Gram-negative bacteria. The analysis of the impact of lonafarnib and tipifarnib on common human pathogens might lead to novel insights into their defense mechanisms and therefore provide new therapeutic targets for antibiotic-resistant bacterial infections.


1999 ◽  
Vol 67 (8) ◽  
pp. 4106-4111 ◽  
Author(s):  
Olga Shamova ◽  
Kim A. Brogden ◽  
Chengquan Zhao ◽  
Tung Nguyen ◽  
Vladimir N. Kokryakov ◽  
...  

ABSTRACT We purified three proline-rich antimicrobial peptides from elastase-treated extracts of sheep and goat leukocytes and subjected two of them, OaBac5α and ChBac5, to detailed analysis. OaBac5α and ChBac5 were homologous to each other and to bovine Bac5. Both exhibited potent, broad-spectrum antimicrobial activity under low-concentration salt conditions. While the peptides remained active againstEscherichia coli, Pseudomonas aeruginosa,Bacillus subtilis, and Listeria monocytogenesin 100 mM NaCl, they lost activity against Staphylococcus aureus and Candida albicans under these conditions. ChBac5 was shown to bind lipopolysaccharide, a property that could enhance its ability to kill gram-negative bacteria. Proline-rich Bac5 peptides are highly conserved in ruminants and may contribute significantly to their innate host defense mechanisms.


1990 ◽  
Vol 258 (1) ◽  
pp. R182-R186 ◽  
Author(s):  
L. Johannsen ◽  
L. A. Toth ◽  
R. S. Rosenthal ◽  
M. R. Opp ◽  
F. Obal ◽  
...  

Bacterial infections and certain muramyl peptides elicit a variety of pathophysiological effects including increases in body temperature and slow-wave sleep. Bacterial cell wall peptidoglycan is composed of muramyl peptides. To investigate the ability of isolated bacterial cell walls to enhance slow-wave sleep, rabbits were injected intravenously with cell walls isolated from Staphylococcus aureus or with soluble peptidoglycan prepared from Neisseria gonorrhoeae. These injections increased slow-wave sleep, electroencephalographic delta-wave amplitudes, and body temperature, reduced rapid-eye-movement sleep, and induced neutrophilia and lymphopenia. The somnogenic and pyrogenic effects of S. aureus cell walls developed within 1 h and persisted throughout the recording period. Injections of N. gonorrhoeae peptidoglycan induced similar effects but of larger magnitude and shorter duration. We conclude that peptidoglycan is a bacterial component that mediates the increased sleep observed during infectious disease.


2019 ◽  
Vol 295 (9) ◽  
pp. 2570-2581 ◽  
Author(s):  
Han Zheng ◽  
Haifeng Li ◽  
Jingyuan Zhang ◽  
Hanlu Fan ◽  
Lina Jia ◽  
...  

Serum amyloid A (SAA), one of the major highly conserved acute-phase proteins in most mammals, is predominantly produced by hepatocytes and also by a variety of cells in extrahepatic tissues. It is well-known that the expression of SAA is sharply increased in bacterial infections. However, the exact physiological function of SAA during bacterial infection remains unclear. Herein, we showed that SAA expression significantly increased in abscesses of Staphylococcus aureus cutaneous infected mice, which exert direct antibacterial effects by binding to the bacterial cell surface and disrupting the cell membrane in acidic conditions. Mechanically, SAA disrupts anionic liposomes by spontaneously forming small vesicles or micelles under acidic conditions. Especially, the N-terminal region of SAA is necessary for membrane disruption and bactericidal activity. Furthermore, we found that mice deficient in SAA1/2 were more susceptible to infection by S. aureus. In addition, the expression of SAA in infected skin was regulated by interleukin-6. Taken together, these findings support a key role of the SAA in host defense and may provide a novel therapeutic strategy for cutaneous bacterial infection.


2013 ◽  
Vol 81 (12) ◽  
pp. 4363-4376 ◽  
Author(s):  
Tyler D. Scherr ◽  
Christelle M. Roux ◽  
Mark L. Hanke ◽  
Amanda Angle ◽  
Paul M. Dunman ◽  
...  

ABSTRACTThe potent phagocytic and microbicidal activities of neutrophils and macrophages are among the first lines of defense against bacterial infections. YetStaphylococcus aureusis often resistant to innate immune defense mechanisms, especially when organized as a biofilm. To investigate howS. aureusbiofilms respond to macrophages and neutrophils, gene expression patterns were profiled using Affymetrix microarrays. The addition of macrophages toS. aureusstatic biofilms led to a global suppression of the biofilm transcriptome with a wide variety of genes downregulated. Notably, genes involved in metabolism, cell wall synthesis/structure, and transcription/translation/replication were among the most highly downregulated, which was most dramatic at 1 h compared to 24 h following macrophage addition to biofilms. Unexpectedly, few genes were enhanced in biofilms after macrophage challenge. Unlike coculture with macrophages, coculture ofS. aureusstatic biofilms with neutrophils did not greatly influence the biofilm transcriptome. Collectively, these experiments demonstrate thatS. aureusbiofilms differentially modify their gene expression patterns depending on the leukocyte subset encountered.


2018 ◽  
Vol 41 (4) ◽  
pp. 353-363
Author(s):  
Alberto J. Valencia-Botin ◽  
Melesio Gutiérrez-Lomelí ◽  
Juan A. Morales-Del-Río ◽  
Pedro J. Guerrero-Medina ◽  
Miguel A. Robles-García ◽  
...  

Actualmente existe la necesidad de hacer frente al problema de la resistencia a los antibióticos y al uso indiscriminado de fungicidas químicos en la agricultura. El objetivo de este trabajo fue evaluar el efecto inhibitorio de extractos acuosos, metanólicos, acetónicos y hexánicos de hoja y tallo de Vitex mollis Kunth (Lamiaceae) contra diferentes bacterias (Escherichia coli, Micrococcus luteus, Salmonella enterica y Staphylococcus aureus) y especies del hongo Fusarium (F. verticillioides, F. oxysporum, F. tapsinum y F. oxysporum f.sp. lycopersici) de importancia en la salud y en la agricultura, así como determinar su composición química general. Se determinaron las concentraciones inhibitorias mínimas (CIM) de todos los extractos por la técnica de microdilución, excepto del hexánico, que no presentó inhibición en las bacterias estudiadas. S. enterica fue la bacteria que mostró mayor sensibilidad al extracto metanólico de tallo (CIM = 28 μg mL-1), le siguieron M. luteus (CIM = 32 μg mL-1), S. aureus (CIM = 75 μg mL-1) y E. coli (CIM = 80 μg mL- 1). Los extractos metanólicos y acuosos de tallo presentaron mayor porcentaje de inhibición contra los diferentes tipos de Fusarium evaluados por el método de dilución en agar. Los extractos de V. mollis inhibieron a F. verticillioides entre 62 y 91 % con 120 μg mL-1 de extracto. El orden de las especies de hongos inhibidas por los extractos fue: F. verticillioides > F. oxysporum > F. tapsinum > F. oxysporum f.sp. lycopersici. La composición química de las especies se determinó mediante pruebas para fenoles, taninos, flavonoides, triterpenos, alcaloides, cumarinas y saponinas. Ninguno de los extractos presentó alcaloides y saponinas. Los fenoles (37.1 mg EAG/g muestra seca) y flavonoides (26.8 mg EQ/g muestra seca) fueron los compuestos mayoritarios en los extractos metanólicos y acuosos. En conclusión, se requieren cantidades muy pequeñas de extracto para la inhibición de bacterias y de Fusarium; por lo tanto, V. mollis puede ser considerada una fuente de metabolitos para este fin y en la agricultura como control alternativo dentro de un manejo integrado de enfermedades.


Sign in / Sign up

Export Citation Format

Share Document