Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes

Mody, Christopher H.; Buser, Deborah E.; Syme, Rachel; Woods, Donald E.

doi:10.1128/iai.63.5.1800-1805.1995

Cited by 27 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, T-cell proliferation to exoenzyme S is not blocked by an anti-DR antibody as is the case with other well-characterized mitogens (39). Previous data which show that greater than 95% of tested adults proliferated to exoenzyme S in vitro are also consistent with a T-cell mitogen (32).…”

Section: Discussionsupporting

confidence: 69%

“…Research has therefore focused on identifying antigenic determinants of the microorganism that are recognized by T cells of normal healthy adults. We have recently reported that a purified preparation of exoenzyme S induces T cells to proliferate in over 95% of adults (32). The high frequency of adult responders suggests that exoenzyme S may be stimulating T cells as a mitogen or superantigen.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pseudomonas aeruginosaExoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

et al. 1998

View full text Add to dashboard Cite

Virtually all cystic fibrosis (CF) patients become infected withPseudomonas aeruginosa, and once the infection is established, the organism is rarely cleared. One of the P. aeruginosa virulence factors, exoenzyme S, has been shown to correlate with increased morbidity and mortality both in rat models of chronic pulmonary inflammation and in human CF patients. It has previously been shown that exoenzyme S is a potent stimulus for the proliferation of T cells in greater than 95% of adults, which could contribute to the pathogenesis of CF. The goal of this study was to determine the mechanism of T-cell stimulation by exoenzyme S in an effort to shed light on the immune response and contribute to understanding its role in P. aeruginosa pathogenesis. The current studies demonstrate that exoenzyme S stimulates naive T cells, since fetal blood lymphocytes proliferated and adult lymphocytes that expressed CD45RA proliferated. The percentage of T cells activated by exoenzyme S after a 4-h culture (as measured by CD69 surface expression) was intermediate in magnitude compared to levels induced by a panel of superantigens and mitogens. To determine the mechanism of activation, the requirement for accessory cells was investigated. The proliferative response to exoenzyme S was dependent on the presence of accessory cells but was not blocked by an anti-DR antibody. Exoenzyme S activated both CD4+ and CD8+ T cells, but CD4+ T cells were preferentially activated. The Vβ repertoire of donor T cells showed no preferential activation or preferential expansion after stimulation by exoenzyme S, suggesting that it is not a superantigen. Taken together, our data suggest that exoenzyme S is a T-cell mitogen but not a superantigen. Activation of a large percentage of T lymphocytes by exoenzyme S may produce a lymphocyte-mediated inflammatory response that should be considered in the pathogenesis of CF.

show abstract

Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

Pseudomonas aeruginosaExoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

et al. 1998

View full text Add to dashboard Cite

show abstract

“…A single nucleotide polymorphism within recipient TLR4 that is associated with decreased sensitivity of TLR4 was found to be protective against ACR [69]. Pseudomonas itself can preferentially cause CD4 T cell activation and proliferation, via exoenzymes such as exotoxin-A, though such exoenzymes may require preprocessing by an appropriate antigen presenting cell [70,71]. Pseudomonas causes an accumulation of lymphocytes in the perivascular space and stimulates T cells to produce both IFN-γ and IL-1, both of which have been associated with allograft rejection.…”

Section: Because Of the Tremendous Infectious Burden Imposed By Bothmentioning

confidence: 99%

Infectious Triggers of Chronic Lung Allograft Dysfunction

Gregson

2016

Curr Infect Dis Rep

View full text Add to dashboard Cite

Survival after lung transplantation is limited in large part due to the high incidence of chronic rejection, known as chronic lung allograft dysfunction (CLAD). Pulmonary infections are a frequent complication in lung transplant recipients, due both to immunosuppressive medications and constant exposure of the lung allograft to the external environment via the airways. Infection is a recognized risk factor for the development of CLAD, and both acute infection and chronic lung allograft colonization with microorganisms increase the risk for CLAD. Acute infection by community acquired respiratory viruses, and the bacteria Pseudomonas aeruginosa and Staphylococcus aureus are increasingly recognized as important risk factors for CLAD. Colonization by the fungus Aspergillus may also augment the risk of CLAD. Fostering this transition from healthy lung to CLAD in each of these infectious episodes is the persistence of an inflammatory lung allograft environment.

show abstract

“…After appropriate consent (approved by the Conjoint Health Research Ethics Board at the University of Calgary), human PBMCs were isolated via Ficol-Hypaque separation from blood of healthy donors as reported previously [44].…”

Section: Antibodies and Antiserummentioning

confidence: 99%

Membrane CD14, but not soluble CD14, is used by exoenzyme S fromP. aeruginosato signal proinflammatory cytokine production

Berenger

Hamill

Stack

et al. 2011

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Recognition of TLR agonists involves a complex interplay among a variety of serum and cell membrane molecules, including mCD14 and sCD14 that is not fully understood. TLR activation results in downstream signaling that induces inflammatory cytokine production in response to pathogenic molecules, such as ExoS, which is a TLR2 and TLR4 agonist produced by the opportunistic pathogen Pseudomonas aeruginosa. We reasoned that responses to ExoS, a protein, might differ from canonical TLR agonists such as LPS. Stimulating the expression of mCD14 with vitamin D3 enhanced the response to ExoS and LPS. Also, blocking anti-CD14 antibody or removing mCD14 using PLC reduced responses to ExoS and LPS. Furthermore, CD14-deficient cells were unable to bind and respond to ExoS, which was restored by stable transfection of mCD14, indicating that mCD14 was required for the response to ExoS. However, addition of sCD14 to culture enhanced responsiveness to LPS but not ExoS. Moreover, the addition of serum did not alter the response to ExoS but enhanced the response to LPS. Despite differences of adaptor molecule use between ExoS and LPS, lipid antagonists that compete for LPS binding to CD14 also inhibited the response to ExoS. These results highlight a fundamental difference between TLR agonists in their requirements for CD14 and serum components. These results suggest that understanding the dissimilarities and targeting overlapping sites of interaction on CD14 may yield a synergistic, clinical benefit during infections where a variety of TLR agonists are present.

show abstract

Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes

Cited by 27 publications

References 37 publications

Pseudomonas aeruginosaExoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

Pseudomonas aeruginosaExoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

Infectious Triggers of Chronic Lung Allograft Dysfunction

Membrane CD14, but not soluble CD14, is used by exoenzyme S fromP. aeruginosato signal proinflammatory cytokine production

Contact Info

Product

Resources

About