The gastrointestinal tract (GI) is the largest immune organ whose function is controlled by a complex network of neurons from the enteric nervous system (ENS) as well as the sympathetic and parasympathetic system. Evolving evidence indicates that cross-communication between gut-innervating neurons and immune cells regulates many essential physiological functions including protection against mucosal infections. We previously demonstrated that following paraoxon treatment, 70 % of the mice were able to survive an oral infection with S. typhimurium, a virulent strain of Salmonella enterica serovar Typhimurium. The present study aims to investigate the effect that rivastigmine, a reversible AChE inhibitor used for the treatment of neurodegenerative diseases, has on the murine immune defenses of the intestinal mucosa. Our findings show that, similar to what is observed with paraoxon, administration of rivastigmine promoted the release of secretory granules from goblet and Paneth cells, resulting in increased mucin layer. Surprisingly, however, and unlike paraoxon, rivastigmine treatment did not affect overall mortality of infected mice. In order to investigate the mechanistic basis for the differential effects observed between paraoxon and rivastigmine, we used multi-color flowcytometric analysis to characterize the immune cell landscape in the intraepithelial (IE) and lamina propria (LP) compartments of intestinal mucosa. Our data indicate that treatment with paraoxon, but not rivastigmine, led to an increase of resident CD3+CD8+ T lymphocytes in the ileal mucosa (epithelium and lamina propria) and CD11b- CD11c+ dendritic cells in the LP. Our findings indicate the requirement for persistent cholinergic pathway engagement to effect a change in the cellular landscape of the mucosal tissue that is necessary for protection against lethal bacterial infections. Moreover, optimal protection requires a collaboration between innate and adaptive mucosal immune responses in the intestine.

Salmonellosis is one of the most common causes of diarrhea, affecting 1/10 of the global population. Salmonellosis outbreaks (SO) pose a severe threat to the healthcare systems of developing regions. To elucidate the patterns of SO in China, we conducted a systematic review and meta-analysis encompassing 1,134 reports across 74 years, involving 89,050 patients and 270 deaths. A rising trend of SO reports has been observed since the 1970s, with most outbreaks occurring east of the Hu line, especially in coastal and populated regions. It is estimated to have an overall attack rate of 36.66% (95% CI, 33.88-39.45%), and antimicrobial resistance towards quinolone (49.51%) and beta-lactam (73.76%) remains high. Furthermore, we developed an online website, the Chinese Salmonellosis Outbreak Database (CSOD), for visual presentation and data-sharing purposes. This study indicated that healthcare-associated SO required further attention, and our study served as a foundational step in pursuing outbreak intervention and prediction.

MccY is a novel, structurally stable microcin with antibacterial activity against Enterobacteriaceae. However, the bioavailability of orally administrated MccY is unknown. This study evaluated the effects of MccY as a antimicrobial on pre-digestion in vitro and its intake, digestion and gut metabolism in vivo. The result of pre-digestion results that MccY maintained its biological activity and was resistant to decomposition. The study established a safe threshold of 4.46-9.92 mg/kg for the MccY dosage-body weight relationship in BALB/c mice. Mice fed with MccY demonstrated improved body weight and intestinal barrier function, accompanied with increased IgM immunogenicity and decreased levels of TNF-α, IL-6, and IL-10 in the intestine. MccY significantly facilitates the growth and activity of probiotics including Lactobacillus, Prevotella, and Bacteroides, and leading to the production of SCFAs and MCFAs during bacterial interactions. Furthermore, MccY effectively protects against the inflammatory response caused by Salmonella Typhimurium infection and effectively clears the Salmonella bacteria from the gut. In conclusion, MccY is seen as a promising new therapeutic target drug for enhancing the intestinal microbe-barrier axis and preventing enteritis.

T lymphocytes and myeloid cells express the immunoglobulin-like glycoprotein cluster of differentiation (CD)101, notably in the gut. Here, we investigated the cell-specific functions of CD101 during dextran sulfate sodium (DSS)-induced colitis and Salmonella enterica Typhimurium infection. Similar to conventional CD101-/- mice, animals with a regulatory T cell-specific Cd101 deletion developed more severe intestinal pathology than littermate controls in both models. While the accumulation of T helper 1 cytokines in a CD101-deficient environment entertained DSS-induced colitis, it impeded the replication of Salmonella as revealed by studying CD101-/- x interferon-g-/- mice. Moreover, CD101-expressing neutrophils were capable to restrain Salmonella infection in vitro and in vivo. Both cell-intrinsic and -extrinsic mechanisms of CD101 contributed to the control of bacterial growth and spreading. The CD101-dependent containment of Salmonella infection required the expression of Irg-1 and Nox2 and the production of itaconate and reactive oxygen species. The level of intestinal microbial antigens in the sera of inflammatory bowel disease patients correlated inversely with the expression of CD101 on myeloid cells, which is in line with the suppression of CD101 seen in mice following DSS application or Salmonella infection. Thus, depending on the experimental or clinical setting, CD101 helps to limit inflammatory insults or bacterial infections due to cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways.

BACKGROUND: By acting as an environmental sensor, the ligand-induced transcription factor aryl hydrocarbon receptor (AhR) regulates acute innate and adaptive immune responses against pathogens. Here, we analyzed the function of AhR in a model for chronic systemic infection with attenuated Salmonella Typhimurium (STM).
METHODS: WT and AhR-deficient mice were infected with the attenuated STM strain TAS2010 and analyzed for bacterial burden, host defense functions and inflammatory stress erythropoiesis.
RESULTS: AhR-deficient mice were highly susceptible to TAS2010 infection compared with WT mice demonstrated by reduced bacterial clearance and increased mortality. STM infection resulted in macrocytic anemia and enhanced splenomegaly along with destruction of the splenic architecture in AhR-deficient mice. In addition, AhR-deficient mice displayed a major expansion of splenic immature red blood cells, indicative of infection-induced stress erythropoiesis. Elevated serum levels of erythropoietin and interleukin-6 upon infection as well as increased numbers of splenic stress erythroid progenitors already in steady state probably drive this effect and might cause the alterations in splenic immune cell compartments, thereby preventing an effective host defense against STM in AhR-deficient mice.
CONCLUSIONS: AhR-deficient mice fail to clear chronic TAS2010 infection due to enhanced stress erythropoiesis in the spleen and accompanying destruction of the splenic architecture.

Non-typhoidal Salmonella typically presents with gastroenteritis. However, an invasive Salmonella infection, which may be typically seen in immunocompromised patients, has a propensity for aortic involvement, especially in patients with risk factors for atherosclerosis. Here we present a 60-year-old female with multiple comorbid conditions and currently on immunosuppressants for rheumatoid arthritis, who presented with nausea, vomiting, and fever of three weeks duration and was found to have Salmonella bacteremia. Blood cultures were positive for Salmonella enterica. Computed tomography (CT) abdomen with contrast was concerning for mycotic aortitis. The patient underwent endovascular repair of an aortic ulcer and was treated with a six-week course of ceftriaxone. Mycotic aneurysm is a rare but potentially fatal complication of invasive Salmonella infection. It occurs typically in older men with atherosclerotic risk factors. It mostly presents as fever, back pain, and/or abdominal pain. Our patient was a middle-aged female who presented with non-specific symptoms. CT angiogram is the diagnostic modality of choice and treatment may require surgical vascular repair and long-term antibiotics. A high level of suspicion is needed to diagnose Salmonella-related mycotic aneurysm/aortitis. Early diagnosis and treatment may improve the mortality.

Thoracic empyema is a collection of infectious material (pus) in the pleural cavity. Salmonella enterica species rarely cause pleuropulmonary infections. This condition poses a significant challenge in diagnosis and management due to its atypical presentation and potential for severe complications. This is a case of an immunocompromised host with glioblastoma who presented with a large loculated fluid collection in the left pleural space. The patient received broad-spectrum antibiotics and underwent urgent chest tube placement and drainage of pus, which grew Salmonella enterica subspecies enterica. He was also found to be bacteremic with the same organism. Subsequently, he underwent video-assisted thoracoscopic surgery (VATS) with decortication and evacuation of the empyema. Even though the prognosis for empyema is generally unfavorable, with increased morbidity and mortality, due to timely intervention, a successful outcome was achieved in this patient with an atypical presentation of salmonella infection.

Salmonella is a gram-negative bacilli bacterium that can infect and colonize humans, causing a wide range of clinical manifestations. The most common manifestation is gastroenteritis, usually after ingestion of undercooked and ill-prepared food, particularly in developing countries. Indonesia is among those reported to have a high incidence of Salmonella infection. Uncommonly, extraintestinal manifestations can affect distant body sites, either during or after the episode of bacteremia. This case report presents a rare case of a healthy 19-year-old female who developed an atypical chest wall abscess colonized by Salmonella in the context of experiencing gastroenteritis three weeks prior on her return from Bali, Indonesia. This case highlights the indolent course associated with a Salmonella chest wall abscess with a discussion of the current literature and management.

Salmonellae, considered among the enteric-fever-causing pathogens, is associated with a range of human infections, including gastroenteritis, bacteremia, and osteomyelitis. Salmonella-induced mesenteric adenitis and terminal ileitis resembling acute appendicitis have been reported in the literature. Here, we present a rare case of a patient presenting with severe acute active ileitis and colitis mimicking Crohn\'s disease with no prior history of inflammatory bowel disease and found to have Salmonella group B bacteremia.

Salmonellosis is a globally extensive food-borne disease, which threatens public health and results in huge economic losses in the world annually. The rising prevalence of antibiotic resistance in Salmonella poses a significant global concern, emphasizing an imperative to identify novel therapeutic agents or methodologies to effectively combat this predicament. In this study, self-assembly hydrogen sulfide (H2S)-responsive nanoprodrugs were fabricated with poly(α-lipoic acid)-polyethylene glycol grafted rhein and geraniol (PPRG), self-assembled into core-shell nanoparticles via electrostatic, hydrophilic and hydrophobic interactions, with hydrophilic exterior and hydrophobic interior. The rhein and geraniol are released from self-assembly nanoprodrugs PPRG in response to Salmonella infection, which is known to produce hydrogen sulfide (H2S). PPRG demonstrated stronger antibacterial activity against Salmonella compared with rhein or geraniol alone in vitro and in vivo. Additionally, PPRG was also able to suppress the inflammation and modulate gut microbiota homeostasis. In conclusion, the as-prepared self-assembly nanoprodrug sheds new light on the design of natural product active ingredients and provides new ideas for exploring targeted therapies for specific Enteropathogens. Graphical  illustration for construction of self-assembly nanoprodrugs PPRG and its antibacterial and anti-inflammatory activities on experimental Salmonella infection in mice.