Neutrophils are innate immune cells that play an essential role during the clearance of pathogens that can release chromatin structures coated by several cytoplasmatic and granular antibacterial ...proteins, called neutrophil extracellular traps (NETs). These supra-molecular structures are produced to kill or immobilize several types of microorganisms, including bacteria and viruses. The contribution of the NET release process (or NETosis) to acute inflammation or the prevention of pathogen spreading depends on the specific microorganism involved in triggering this response. Furthermore, studies highlight the role of innate cells different from neutrophils in triggering the release of extracellular traps during bacterial infection. This review summarizes the contribution of NETs during bacterial and viral infections, explaining the molecular mechanisms involved in their formation and the relationship with different components of such pathogens.
Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn's disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in ...these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.
Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The ...enzymatic reaction catalyzed by HMOX1 generates Fe
, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.
Salmonella enterica
is a common source of food and water-borne infections, causing a wide range of clinical ailments in both human and animal hosts. Immunity to
Salmonella
involves an interplay ...between different immune responses, which are rapidly initiated to control bacterial burden. However,
Salmonella
has developed several strategies to evade and modulate the host immune responses. In this sense, the main knowledge about the pathogenicity of this bacterium has been obtained by the study of mouse models with non-typhoidal serovars. However, this knowledge is not representative of all the pathologies caused by non-typhoidal serovars in the human. Here we review the most important features of typhoidal and non-typhoidal serovars and the diseases they cause in the human host, describing the virulence mechanisms used by these pathogens that have been identified in different models of infection.
Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found ...in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune ...responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.
Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could ...promote the onset and exacerbation of these diseases. Here, we evaluated whether
serovar Typhimurium (
. Typhimurium) infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of
. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS) and interleukin (IL)-10
mice, which develop spontaneous intestinal inflammation. We observed that
. Typhimurium infection makes DSS-treated and IL-10
mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of
. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by
Pathogenicity Island 2-encoded type three secretion system (TTSS-2). Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10
mice susceptibility to develop intestinal inflammation due to previous
. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent
. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.
Inflammatory bowel disease (IBD) includes a set of pathologies that result from a deregulated immune response that may affect any portion of the gastrointestinal tract. The most prevalent and defined ...forms of IBD are Crohn's disease and ulcerative colitis. Although the etiology of IBD is not well defined, it has been suggested that environmental and genetic factors contribute to disease development and that the interaction between these two factors can trigger the pathology. Diet, medication use, vitamin D status, smoking, and bacterial infections have been proposed to influence or contribute to the onset or development of the disease in susceptible individuals. The infection with pathogenic bacteria is a key factor that can influence the development and severity of this disease. Here, we present a comprehensive review of studies performed in human and mice susceptible to IBD, which supports the notion that infection with bacterial pathogens, such as
, could promote the onset of IBD due to permanent changes in the intestinal microbiota, disruption of the epithelial barrier and alterations of the intestinal immune response after infection.
Carbapenem-resistant
ST258 (CRKP-ST258) are a global concern due to their rapid dissemination, high lethality, antibiotic resistance and resistance to components of the immune response, such as ...neutrophils. Neutrophils are major host mediators, able to kill well-studied and antibiotic-sensitive laboratory reference strains of
. However, CRKP-ST258 are able to evade neutrophil phagocytic killing, persisting longer in the host despite robust neutrophil recruitment. Here, we show that neutrophils are unable to clear a CRKP-ST258 isolate (KP35). Compared to the response elicited by a prototypic
ATCC 43816 (KPPR1), the neutrophil intracellular response against KP35 is characterized by equivalent production of reactive oxygen species (ROS) and myeloperoxidase content, but impaired phagosomal acidification. Our results ruled out that this phenomenon is due to a phagocytosis defect, as we observed similar efficiency of phagocytosis by neutrophils infected with KP35 or KPPR1. Genomic analysis of the
loci of KPPR1 and KP35 suggest that the capsule composition of KP35 explain the high phagocytosis efficiency by neutrophils. Consistent with other reports, we show that KP35 did not induce DNA release by neutrophils and KPPR1 only induced it at 3 h, when most of the bacteria have already been cleared. l-arginine metabolism has been identified as an important modulator of the host immune response and positively regulate T cells, macrophages and neutrophils in response to microbes. Our data show that l-arginine supplementation improved phagosome acidification, increased ROS production and enhanced nitric oxide consumption by neutrophils in response to KP35. The enhanced intracellular response observed after l-arginine supplementation ultimately improved KP35 clearance
. KP35 was able to dysregulate the intracellular microbicidal machinery of neutrophils to survive in the intracellular environment. This process, however, can be reversed after l-arginine supplementation.
An effective pathogen has the ability to evade the immune response. The strategies used to achieve this may be based on the direct action of virulence factors or on the induction of host factors. ...Myeloid‐derived suppressor cells (MDSCs) are immune cells with an incredible ability to suppress the inflammatory response, which makes them excellent targets to be exploited by pathogenic bacteria, viruses, or parasites. In this review, we describe the origin and suppressive mechanisms of MDSCs, as well as their role in chronic bacterial, viral, and parasitic infections, where their expansion seems to be essential in the chronicity of the disease. We also analyze the disadvantages of current MDSC depletion strategies and the different in vitro generation methods, which can be useful tools for the deeper study of these cells in the context of microbial infections.
Myeloid‐derived suppressor cells, their mechanisms to suppress the immune response during bacterial, viral, and parasitic infections and current methodologies to study them.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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