SALMONELLA

Salmonella enterica abortusovis is able during the infection to hide itself to the host immune system using unknown mechanisms

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Abortion in sheep due to Salmonella enterica subspecies enterica serovar Abortusovis is an important animal health problem in areas of the Mediterranean, where the sheep industry has a significant economy impact. The pathogen is host restricted to ovines where it invades the intestinal epithelium and causes a systemic infection that often goes undetected, until it manifest as an abortion. In animals that are not pregnant, there are no overt signs of disease, suggesting that the organism can evade detection by the innate immune system during invasion, but the underlying mechanisms are currently unknown. The long-term goal of this study is to elucidate mechanisms involved in the pathogenesis of S. Abortusovis infection. Our central hypothesis is that S. Abortusovis prevents recognition through Toll-like receptors, which renders the host unable to control infection before pathogens reach the uterus and cause abortions. We will contrast S. Abortusovis to a closely related pathogen, S. enterica serovar Typhimurium , whose invasion of the intestinal epithelium is detected by the innate immune system, resulting in overt signs of disease associated with intestinal inflammation. Aim 1, we will determine whether S. Abortusovis evades recognition by TLR5 during invasion of the intestinal epithelium. Aim 2, we will determine whether S. Abortusovis evades recognition by TLR4 during its persistence in tissue macrophages. The proposed studies will take an innovative approach that links clinical observations to molecular virulence mechanisms. By establishing these connections, our studies are to demonstrate that innate immune evasion is a S. Abortusovis-specific virulence mechanism that can explain S. Abortusovis infection in sheep differs drastically from gastroenteritis caused by S. Typhimurium. This outcome is significant because it will establish a new paradigm in Salmonella pathogenesis, which is expected to have a measurable impact on the field of bacterial pathogenesis.'

Introduzione (Teaser)

Salmonella (S) are gram-negative bacteria that invade the intestine, stimulating the innate immune system and causing a massive intestinal inflammatory response called gastroenteritis. However, a few S species variants cause systemic infections that differ dramatically in their clinical presentation and do not cause inflammation.

Descrizione progetto (Article)

Abortion can occur in sheep due to infection from S enterica subspecies Abortusovis. This is an animal health problem that needs to be addressed, particularly in areas, where the sheep industry has a significant economic impact. This pathogen is able to evade detection by the host's innate immune system but the underlying evasive mechanisms are currently unknown. The long-term goal of EU-funded SALMONELLA project is to elucidate mechanisms involved in the pathogenesis of S. Abortusovis infection.

Comparison between different S varieties suggests that persistence of S.Abortusovis can be based on circumvention of immune protective response. Translocation of bacteria from the intestinal lumen is detected by the immune system through pattern-recognition receptors, including so-called toll-like receptors (TLRs). These pattern-recognition receptors are able to recognise microbe-associated molecular patterns that distinguish bacteria from viral or parasitic agents.

A comparison of the symptoms caused by S. Abortusovis and S. Typhimurium revealed striking differences. Intestinal inflammation and diarrhoea were absent from the intestine of animals infected with S. Abortusovis. However, S. Abortusovis was able to chronically persist at the sites of infection, resulting in abortion. Thus, the central hypothesis of the project was that direct contact of S. Abortusovis with the cell does not trigger an innate immune response to control infection.

For the first time ever, the interaction between S. Abortusovis and TLRs was studied. Experiments with a cell line transfected with human TLRs show reduced production of inflammation factors in response to S. Abortusovis in contrast to S. Typhimurium. These results were confirmed using cells transfected with the ovine TLRs. This data will be used soon for eventual publication.

The results of the SALMONELLA project provide an important mechanistic insight into how S. Abortusovis is able to modulate host responses and evade detection. This could lead to the development of novel pathogen detection and treatment options for such diseases with important implications for the sheep industry.