scholarly journals Autoimmunity increases susceptibility to and mortality from sepsis

2021 ◽  
Author(s):  
Isaac J Jensen ◽  
Samantha N Jensen ◽  
Patrick W McGonagill ◽  
Thomas S Griffith ◽  
Ashutosh K Mangalam ◽  
...  

Our prior publication detailing how sepsis influences subsequent development of EAE presented a conceptual advance in understanding the post-sepsis chronic immunoparalysis state (Jensen et al., 2020). However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. Herein, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis incidence among MS, relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis well-established murine models of MS and sepsis, EAE and CLP, respectively, were utilized. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and S. pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.

1999 ◽  
Vol 20 (12) ◽  
pp. 793-797 ◽  
Author(s):  
M. Sigfrido Rangel-Frausto ◽  
Paul Rhomberg ◽  
Richard J. Hollis ◽  
Michael A. Pfaller ◽  
Richard P. Wenzel ◽  
...  

AbstractObjective:To describe the molecular epidemiology ofLegionella pneumophilainfections in the University of Iowa Hospitals and Clinics (UIHC).Design:Molecular epidemiological study using pulsed-field gel electrophoresis (PFGE).Setting:A large university teaching hospital.Isolates:All surviving isolates obtained from culture-proven nosocomialL pneumophilainfections and all surviving isolates obtained from the University of Iowa Hospital and Clinics' water supply between 1981 and 1993.Results:Thirty-three isolates from culture-proven nosocomial cases ofL pneumophilapneumonia were available for typing. PFGE of genomic DNA from the clinical isolates identified six different strains. However, only strain C (16 cases) and strain D (13 cases) caused more than 1 case. Strain C caused clusters of nosocomial infection in 1981, 1986, and 1993 and also caused 4 sporadic cases. Strain D caused a cluster in 1987 and 1988 plus 4 sporadic cases. Of the six strains causing clinical infections, only strains C and D were identified in water samples. PFGE identified three strains in the water supply, of which strains C and D caused clinical disease and also persisted in the water supply during most of the study period.Conclusion:Specific strains ofL pneumophilacan colonize hospital water supplies and cause nosocomial infections over long periods of time.


2020 ◽  
Vol 32 (1) ◽  
pp. 69-85
Author(s):  
Juan de Dios Ruiz-Rosado ◽  
Frank Robledo-Avila ◽  
Hanna Cortado ◽  
Javier Rangel-Moreno ◽  
Sheryl S. Justice ◽  
...  

BackgroundIn children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis–driven renal scarring remain unknown.MethodsWe used a preclinical model of uropathogenic Escherichia coli–induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring.ResultsWe found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli–induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium.ConclusionsThese findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.


1999 ◽  
Vol 24 (1) ◽  
pp. 31-65 ◽  
Author(s):  
Mary S. Berg ◽  
Kendal D. Davenport ◽  
Melanie Dreher ◽  
Jane Greiner ◽  
R. Edward Howell ◽  
...  

2013 ◽  
Vol 01 (02) ◽  
pp. 067-072
Author(s):  
Baljeet Singh ◽  
Avnika Garg ◽  
Nandini Nayyar ◽  
Alka Sharma

AbstractPeriodontal disease may be regarded as a range of different diseases for which certain individuals are at relatively high risk. Epidemiological and molecular studies of the oral microbial flora suggest, that although microbial factors are required for periodontal disease, they alone do not predict the presence or severity of periodontitis. So in high-risk patient groups, host factors appear to play an important role in susceptibility to periodontitis. In recent years elements of host susceptibility, such as immune response and systemic disease state, and other non-microbial environmental factors, such as smoking, have been shown to be important contributors to the disease expression. Thus, periodontitis represents a lifelong account of interactions between our genome, our behavior, and our environment.


Author(s):  
J. K. Maurin

Conductor, resistor, and dielectric patterns of microelectronic device are usually defined by exposure of a photosensitive material through a mask onto the device with subsequent development of the photoresist and chemical removal of the undesired materials. Standard optical techniques are limited and electron lithography provides several important advantages, including the ability to expose features as small as 1,000 Å, and direct exposure on the wafer with no intermediate mask. This presentation is intended to report how electron lithography was used to define the permalloy patterns which are used to manipulate domains in magnetic bubble memory devices.The electron optical system used in our experiment as shown in Fig. 1 consisted of a high resolution scanning electron microscope, a computer, and a high precision motorized specimen stage. The computer is appropriately interfaced to address the electron beam, control beam exposure, and move the specimen stage.


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