scholarly journals Staphylococcus aureus lipoproteins promote abscess formation in mice, shielding bacteria from immune killing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Majd Mohammad ◽  
Manli Na ◽  
Zhicheng Hu ◽  
Minh-Thu Nguyen ◽  
Pradeep Kumar Kopparapu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Lesion Size ◽  
Abscess Formation ◽  
Skin Infections ◽  
Human Immune System ◽  
Immune Evasion Mechanism ◽  
Human Immune

AbstractDespite being a major bacterial factor in alerting the human immune system, the role of Staphylococcus aureus (S. aureus) lipoproteins (Lpp) in skin infections remains largely unknown. Here, we demonstrated that subcutaneous injection of S. aureus Lpp led to infiltration of neutrophils and monocytes/macrophages and induced skin lesions in mice. Lipid-moiety of S. aureus Lpp and host TLR2 was responsible for such effect. Lpp-deficient S. aureus strains exhibited smaller lesion size and reduced bacterial loads than their parental strains; the altered phenotype in bacterial loads was TLR2-independent. Lpp expression in skin infections contributed to imbalanced local hemostasis toward hypercoagulable state. Depletion of leukocytes or fibrinogen abrogated the effects induced by Lpp in terms of skin lesions and bacterial burden. Our data suggest that S. aureus Lpp induce skin inflammation and promote abscess formation that protects bacteria from innate immune killing. This suggests an intriguing bacterial immune evasion mechanism.

scholarly journals Phosphorus Dendrimers as Nanotools against Cancers

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3333 ◽  
Author(s):  
Anne-Marie Caminade
Keyword(s):  
Cell Death ◽  
Small Molecules ◽  
Cytotoxic Effect ◽  
Positive Influence ◽  
Human Immune System ◽  
The Third ◽  
Cancerous Cell ◽  
Human Immune ◽  
Cancerous Cells

This review concerns the use of dendrimers, especially of phosphorhydrazone dendrimers, against cancers. After the introduction, the review is organized in three main topics, depending on the role played by the phosphorus dendrimers against cancers: (i) as drugs by themselves; (ii) as carriers of drugs; and (iii) as indirect inducer of cancerous cell death. In the first part, two main types of phosphorus dendrimers are considered: those functionalized on the surface by diverse organic derivatives, including known drugs, and those functionalized by diverse metal complexes. The second part will display the role of dendrimers as carriers of anticancer “drugs”, which can be either small molecules or anticancer siRNAs, or the combination of both. In the third part are gathered a few examples of phosphorhydrazone dendrimers that are not cytotoxic by themselves, but which under certain circumstances induce a cytotoxic effect on cancerous cells. These examples include a positive influence on the human immune system and the combination of bioimaging with photodynamic therapy properties.

scholarly journals Role of Neutrophil Leukocytes in Cutaneous Infection Caused by Staphylococcus aureus

2000 ◽  
Vol 68 (11) ◽  
pp. 6162-6167 ◽  
Author(s):  
Lena Mölne ◽  
Margareta Verdrengh ◽  
Andrzej Tarkowski
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibody ◽  
Great Majority ◽  
Skin Lesions ◽  
Protective Role ◽  
Toxic Shock ◽  
Cutaneous Infections ◽  
High Prevalence ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Despite the high prevalence of cutaneous infections, little is known about the role of host immune responsiveness duringStaphylococcus aureus dermatitis. We have recently described a murine model of infectious dermatitis induced by superantigen-producing S. aureus. To assess the role of neutrophils in staphylococcal dermatitis, mice were given granulocyte-depleting monoclonal antibody prior to and on several occasions following intracutaneous inoculation with staphylococci. The granulocyte-depleted mice that had been intradermally inoculated withS. aureus developed crusted ulcerations which tended not to heal, whereas animals injected with control monoclonal antibody displayed only minor and transient skin lesions. The finding of severe ulcerations in neutropenic mice correlated with a significantly higher burden of bacteria in the blood and skin during the early phase of the infection. Importantly, while mice with an intact granulocyte population showed only limited skin infection, bacteremia occurred in the great majority of the neutrophil-depleted animals. As a consequence, the latter individuals exhibited significantly increased levels of the proinflammatory cytokine interleukin-6 and specific antibodies to staphylococcal cell wall components and toxic shock syndrome toxin-1 in the serum. Our data point to a crucial protective role of granulocytes in S. aureus dermatitis.

scholarly journals Skin Associated Staphylococcus Aureus Contributes to Disease Progression in CTCL

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 659-659
Author(s):  
Cosmin A Tegla ◽  
Alberto M Herrera ◽  
Angelina M Seffens ◽  
Melania H Fanok ◽  
George Dean ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
T Lymphocytes ◽  
Disease Progression ◽  
Clinical Score ◽  
Skin Lesions ◽  
Skin Microbiome ◽  
Effect Relationship ◽  
Skin Flora

It has been proposed that bacteria play a direct role in progression of cutaneous T cell lymphoma (CTCL), although definitive evidence is missing, and the underlying mechanism of how microbes contribute to disease progression remains unknown. The skin of CTCL patients is frequently colonized with Staphylococcus aureus (S. aureus) strains and infections with hospital and community associated strains of S. aureus are a frequent cause of morbidity and mortality among patients with advanced CTCL. Here we provide a comprehensive analysis of the association between CTCL and S. aureus colonization, and use our unique pre-clinical animal model of CTCL to determine the cause-effect relationship between skin-associated S. aureus and CTCL progression. To understand the relationship between bacterial colonization and CTCL we collected skin swabs from active lesions, unaffected skin and nares of CTCL patients to perform S. aureus cultures and 16S rRNA gene sequencing. Skin swabs of psoriasis patients and healthy donors served as controls. The frequency of S. aureus colonization determined by culture based techniques revealed that >65% of advanced stage patients had S. aureus present at lesional/tumor sites, while corresponding sites in patients with psoriasis and in healthy controls rarely had detectable S. aureus. Colonization rates correlated positively with the disease stage. Unbiased, 16s sequencing based analysis of the skin microbiome from advanced CTCL patients revealed that the overall skin microbiome of these patients is distinct from that of healthy individuals and patients with psoriasis. A lower phylogenetic diversity and significantly higher relative abundance of Staphylococcus species was found in CTCL patients. To determine the causal relationship between skin flora and progression of CTCL we used our mouse model of CTCL and assessed disease progression in both conventionally housed specific-pathogen-free (SPF) conditions and in germ free (GF) isolators using a standardized clinical score. The CD4CreSTAT3stopfl/+ mice express a hyper-active STAT3C mutant protein selectively in T lymphocytes and virtually all mutant mice develop T cell infiltration in the epidermis causing skin lesions resembling CTCL, by eight months of age. In contrast to the SPF housed animals, GF mice remained disease free or developed only a mild phenotype (clinical score 1 out of 5) after 11 months of follow-up. Notably, when GF CD4CreSTAT3stopfl/+ mice were transitioned to SPF conditions they all developed advanced disease. Finally, we examined the role of T cell antigen receptor (TCR) signaling in mediating the transformation of T lymphocytes. R26STAT3Cstopfl/+CD4Cre Rag2KO OTII mice express only OVA-specific TCRs. T cells from R26STAT3Cstopfl/+ CD4Cre Stim1fl/fl mice express a normal TCR repertoire, but exhibit defective T cell receptor signaling due to compromised calcium influx. Both strains failed to develop typical skin lesions, suggesting an essential role for TCR interaction with tumor microenvironment and microbial antigens in the pathogenesis of CTCL. In conclusion, we demonstrate a strong correlation between CTCL staging and rates of S. aureus colonization. Our study supports a cause-effect relationship between skin flora and CTCL oncogenesis. We propose that CTCL represents an antigen driven malignancy. Further studies using mono-colonization with single bacterial strains are needed to further interrogate the role of specific bacteria. Disclosures Hymes: Celgene: Consultancy. Odum:Micreos human Health B.V: Consultancy. Geskin:Merck: Other: Supported/Contracted Research; UpToDate: Patents & Royalties: Royalty, Receipt of Intellectual Property Rights / Patent Holder; Mallinckrodt: Consultancy, Honoraria, Other: Supported/Contracted Research; Helsinn: Consultancy, Honoraria, Other: Supported/Contracted Research; Stratpharma: Other: Supported/Contracted Research; Medivir: Consultancy, Honoraria; Medscape: Speakers Bureau; Actelion: Other: Supported/Contracted Research.

Epidemic Bullous Impetigo in a Nursery Due to a Nasal Carrier of Staphylococcus aureus: Role of Epidemiology and Control Measures

1984 ◽  
Vol 5 (7) ◽  
pp. 326-331 ◽  
Author(s):  
Allyn K. Nakashima ◽  
James R. Allen ◽  
William J. Martone ◽  
Brian D. Plikaytis ◽  
Beth Storer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Phage Type ◽  
Skin Lesions ◽  
Control Measures ◽  
Epidemic Strain ◽  
Nasal Carrier ◽  
Infection Control Measures ◽  
Epidemic Period ◽  
And Control

AbstractFrom September 14, 1981 to February 28, 1982, an epidemic of bullous impetigo caused by a penicillin/tetracycline resistant strain of Staphylococcus aureus, phage type 3A/3C, occurred in a newborn nursery in Louisville, Kentucky. Twenty of 1,181 (1.7%) infants at risk developed disease during the six-month epidemic period. Clinically all case-infants had bullous impetigo skin lesions. One infant developed staphylococcal septicemia. No infant died. An epidemiologic investigation identified a nurse as having significantly greater contact with case-infants than control-infants (p=0.0013). She was also found to be a nasal carrier of the epidemic strain. Infection control measures appeared to decrease infant-to-infant transmission via the hands of non-colonized nurses, but did not affect transmission from the nurse carrying the epidemic strain to infants. No cases of bullous impetigo have occurred since this nurse was temporarily removed from the nursery for treatment.

scholarly journals Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice

2021 ◽  
Vol 119 ◽  
pp. 102612
Author(s):  
Mohsen Khosravi-Maharlooei ◽  
HaoWei Li ◽  
Markus Hoelzl ◽  
Guiling Zhao ◽  
Amanda Ruiz ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Human Immune System ◽  
Human Immune

scholarly journals Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development

2020 ◽  
Author(s):  
Tiina E. Kähkönen ◽  
Jussi M. Halleen ◽  
Jenni Bernoulli
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Efficacy And Safety ◽  
Human Immune System ◽  
Oncology Research ◽  
Preclinical Drug Development ◽  
Metastatic Process ◽  
Human Immune ◽  
Species Specific

Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.

SKIN INFECTIONS AND ACUTE NEPHRITIS IN AMERICAN INDIAN CHILDREN

PEDIATRICS ◽  
1967 ◽  
Vol 39 (2) ◽  
pp. 263-279
Author(s):  
Bascom F. Anthony ◽  
Lawrence V. Perlman ◽  
Lewis W. Wannamaker
Keyword(s):  
Normal Population ◽  
Skin Lesions ◽  
Skin Infections ◽  
Upper Respiratory Tract ◽  
Indian Children ◽  
Superficial Skin ◽  
Group A ◽  
Relationship Of ◽  
The Relationship

Serial observations were obtained over an 18-month period of 270 Indian children with pyoderma. Beta-hemolytic streptococci, predominantly group A, and coagulasepositive staphylococci were recovered from the majority of lesions (80% and 70%, respectively), both on the initial and on subsequent cultures. The predominant agglutination patterns of streptococcal strains were similar to those described in other studies of superficial skin infections. Another agglutination pattern, 17/23/47, not previously observed to be prevalent in streptococci from skin lesions, was identified in a significant number of skin cultures. In addition, the hitherto undescribed association of M-types, including type 41 and a new M-type, with strains of T-agglutination pattern 3/13/B3264 was found. In striking contrast to the streptococcal strains, established "impetigo" strains of Staph. aureus (type 71 or other group II strains) were in the minority. Throat cultures of children with pyoderma suggested a limited relationship between infection or colonization of the pharynx and infection of the skin, while nasal streptococci were more closely correlated with and possibly derived from the flora of the skin lesions. Titers of ASO were not often elevated over control values in children with pyoderma, while anti-DNAse B titers were more commonly increased. Group A streptococci isolated from skin lesions prior to or at the time acute nephritis was recognized included type 12 (M and T) and strains classified by T-agglutination as 5/27/44, 11 and 4. The role of infection or colonization of the upper respiratory tract in the relationship of pyoderma to nephritis was not clarified in these studies. Moreover, in view of the frequency of change of group A streptococcal strains in skin lesions, as shown in serial observations in this study, the nephritogenic significance of streptococci recovered from skin lesions at the time of recognition of nephritis must remain in some doubt. Questions concerning the pathogenesis of endemic nephritis associated with pyoderma can probably be most reliably answered by frequent, prospective observations of a normal population with significant occurrence of streptococcal skin infections.

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