scholarly journals Cytochromes c Constitute a Layer of Protection against Nitric Oxide but Not Nitrite

2018 ◽  
Vol 84 (17) ◽  
Author(s):  
Qiu Meng ◽  
Yijuan Sun ◽  
Haichun Gao
Keyword(s):  
Nitric Oxide ◽  
Specific Activity ◽  
Shewanella Oneidensis ◽  
Main Role ◽  
Content Type ◽  
Environmental Bacterium ◽  
Enzymatic Systems ◽  
Bacteriostatic Agent ◽  
Protective Proteins

ABSTRACT Nitric oxide (NO) is a radical gas that reacts with various biological molecules in complex ways to inhibit growth as a bacteriostatic agent. NO is nearly ubiquitous because it can be generated both biotically and abiotically. To protect the cell from NO damage, bacteria have evolved many strategies, with the production of detoxifying enzymatic systems being the most efficient. Here, we report that c-type cytochromes (cytochromes c) constitute a primary NO protection system in Shewanella oneidensis, a Gram-negative environmental bacterium renowned for respiratory versatility due to its high cytochrome c content. By using mutants producing cytochromes c at varying levels, we found that the content of these proteins is inversely correlated with the growth inhibition imposed by NO, whereas the effect of each individual cytochrome c is negligible. This NO-protecting system has no effect on nitrite inhibition. In the absence of cytochromes c, other NO targets and protective proteins, such as NnrS, emerge to show physiological influences during the NO stress. We further demonstrate that cytochromes c also play a similar role in Escherichia coli, albeit only modestly. Our data thus identify the in vivo function of an important group of proteins in alleviating NO stress. IMPORTANCE It is widely accepted that the antibacterial effects of nitrite are attributable to nitric oxide (NO) formation, suggesting a correlation of bacterial susceptibilities to these two chemicals. However, compared to E. coli, S. oneidensis is highly sensitive to nitrite but resistant to NO, implying the presence of robust NO-protective systems. Here, we show that c-type cytochromes (cytochromes c) play a main role in protecting S. oneidensis against damages from NO but not from nitrite. In their absence, impacts of proteins that promote NO tolerance and that are targets of NO inhibition become evident. Our data thus reveal the specific activity of cytochromes c in alleviating the stress caused by NO but not nitrite.

scholarly journals Distinct Nitrite and Nitric Oxide Physiologies inEscherichia coliandShewanella oneidensis

2018 ◽  
Vol 84 (12) ◽  
pp. e00559-18 ◽  
Author(s):  
Qiu Meng ◽  
Jianhua Yin ◽  
Miao Jin ◽  
Haichun Gao
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Growth Inhibition ◽  
Shewanella Oneidensis ◽  
Food Preservation ◽  
Content Type ◽  
E Coli ◽  
Cell Extracts ◽  
Copper Oxidase

ABSTRACTNitrite has been used as a bacteriostatic agent for centuries in food preservation. It is widely accepted that this biologically inert molecule functions indirectly, serving as a stable reservoir of bioactive nitric oxide (NO) and other reactive nitrogen species to impact physiology. As a result, to date, we know surprisingly little aboutin vivotargets of nitrite. Here, we carry out comparative analyses of nitrite and NO physiology inEscherichia coliand inShewanella oneidensis, a Gram-negative environmental bacterium renowned for respiratory versatility. These two bacteria differ from each other in many aspects of nitrite and NO physiology, including NO generation, NO degradation, and unexpectedly, their contrary susceptibility to nitrite and NO. In cell extracts of both bacteria, most of the NO targets are also susceptible to nitrite, and vice versa. However, with respect to growth inhibition caused by NO, the targets are impacted distinctly; NO targets are responsible for the inhibition of growth ofE. colibut not ofS. oneidensis. More surprisingly, all proteins identified to be implicated in NO tolerance in other bacteria appear to play a dispensable role in protectingS. oneidensisagainst NO. These data suggest thatS. oneidensisis equipped with a robust but yet unknown NO protecting system. In the case of nitrite, it is clear that the target of physiological significance in both bacteria is cytochrome heme-copper oxidase.IMPORTANCENitrite is toxic to living organisms at high levels, but such antibacterial effects of nitrite are attributable to the formation of nitric oxide (NO), a highly reactive radical gas molecule. Here, we report thatShewanella oneidensisis highly resistant to NO but sensitive to nitrite compared toEscherichia coliby approximately 4-fold. In both bacteria, nitrite inhibits bacterial growth by targeting cytochrome heme-copper oxidase. In contrast, the targets of NO are diverse. Although these targets are similar inE. coliandS. oneidensis, they are responsible for growth inhibition caused by NO in the former but not in the latter. Overall, the presented data, along with the previous data, solidify a proposal that thein vivotargets of NO and nitrite in bacteria are largely different.

scholarly journals Interplay of Nitric Oxide Synthase (NOS) and SrrAB in Modulation ofStaphylococcus aureusMetabolism and Virulence

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Kimberly L. James ◽  
Austin B. Mogen ◽  
Jessica N. Brandwein ◽  
Silvia S. Orsini ◽  
Miranda J. Ridder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Double Mutant ◽  
Nitrate Assimilation ◽  
Arginine Deiminase ◽  
Growth Defect ◽  
Content Type ◽  
Metabolic Versatility ◽  
Oxide Synthase

ABSTRACTStaphylococcus aureusnitric oxide synthase (saNOS) is a major contributor to virulence, stress resistance, and physiology, yet the specific mechanism(s) by which saNOS intersects with other known regulatory circuits is largely unknown. The SrrAB two-component system, which modulates gene expression in response to the reduced state of respiratory menaquinones, is a positive regulator ofnosexpression. Several SrrAB-regulated genes were also previously shown to be induced in an aerobically respiringnosmutant, suggesting a potential interplay between saNOS and SrrAB. Therefore, a combination of genetic, molecular, and physiological approaches was employed to characterize anos srrABmutant, which had significant reductions in the maximum specific growth rate and oxygen consumption when cultured under conditions promoting aerobic respiration. Thenos srrABmutant secreted elevated lactate levels, correlating with the increased transcription of lactate dehydrogenases. Expression of nitrate and nitrite reductase genes was also significantly enhanced in thenos srrABdouble mutant, and its aerobic growth defect could be partially rescued with supplementation with nitrate, nitrite, or ammonia. Furthermore, elevated ornithine and citrulline levels and highly upregulated expression of arginine deiminase genes were observed in the double mutant. These data suggest that a dual deficiency in saNOS and SrrAB limitsS. aureusto fermentative metabolism, with a reliance on nitrate assimilation and the urea cycle to help fuel energy production. Thenos,srrAB, andnos srrABmutants showed comparable defects in endothelial intracellular survival, whereas thesrrABandnos srrABmutants were highly attenuated during murine sepsis, suggesting that SrrAB-mediated metabolic versatility is dominantin vivo.

scholarly journals Intracellular NADPH Levels Affect the Oligomeric State of the Glucose 6-Phosphate Dehydrogenase

2012 ◽  
Vol 11 (12) ◽  
pp. 1503-1511 ◽  
Author(s):  
Michele Saliola ◽  
Angela Tramonti ◽  
Claudio Lanini ◽  
Samantha Cialfi ◽  
Daniela De Biase ◽  
...  
Keyword(s):  
Specific Activity ◽  
Kluyveromyces Lactis ◽  
Growth Conditions ◽  
G6pdh Activity ◽  
Oligomeric State ◽  
Content Type ◽  
Metabolic Role ◽  
Activity Band ◽  
Glucose 6 Phosphate Dehydrogenase

ABSTRACTIn the yeastKluyveromyces lactis, glucose 6-phosphate dehydrogenase (G6PDH) is detected as two differently migrating forms on native polyacrylamide gels. The pivotal metabolic role of G6PDH inK. lactisled us to investigate the mechanism controlling the two activities in respiratory and fermentative mutant strains. An extensive analysis of these mutants showed that the NAD+(H)/NADP+(H)-dependent cytosolic alcohol (ADH) and aldehyde (ALD) dehydrogenase balance affects the expression of the G6PDH activity pattern. Under fermentative/ethanol growth conditions, the concomitant activation of ADH and ALD activities led to cytosolic accumulation of NADPH, triggering an alteration in the oligomeric state of the G6PDH caused by displacement/release of the structural NADP+bound to each subunit of the enzyme. The new oligomeric G6PDH form with faster-migrating properties increases as a consequence of intracellular redox unbalance/NADPH accumulation, which inhibits G6PDH activityin vivo. The appearance of a new G6PDH-specific activity band, following incubation ofSaccharomyces cerevisiaeand human cellular extracts with NADP+, also suggests that a regulatory mechanism of this activity through NADPH accumulation is highly conserved among eukaryotes.

scholarly journals Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

2013 ◽  
Vol 82 (1) ◽  
pp. 233-242 ◽  
Author(s):  
Zachary T. Cusumano ◽  
Michael E. Watson ◽  
Michael G. Caparon
Keyword(s):  
Nitric Oxide ◽  
Innate Immunity ◽  
Streptococcus Pyogenes ◽  
Murine Model ◽  
Acid Stress ◽  
Arginine Deiminase ◽  
Content Type ◽  
Cutaneous Tissue

ABSTRACTA bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogenStreptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stressin vitro. Its expression is enhanced in murine models of infection, suggesting an important rolein vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS−/−) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability ofS. pyogenesto utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by whichS. pyogenesuses its metabolism to modulate innate immunity through depletion of an essential host nutrient.

Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates

1996 ◽  
Vol 84 (1) ◽  
pp. 71-78 ◽  
Author(s):  
B. Gregory Thompson ◽  
Ryszard M. Pluta ◽  
Mary E. Girton ◽  
Edward H. Oldfield
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
No Production ◽  
Direct Role ◽  
Content Type ◽  
Continuous Release ◽  
Fine Print

✓ The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either l-n-monomethyl arginine or nitro l-arginine. During basal conditions (PaCO2 of 38–42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p < 0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of l-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 ± 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypotension is not mediated by NO; and increasing PaCO2 induces increased NO production.

scholarly journals Improving Arsenic Tolerance of Pyrococcus furiosus by Heterologous Expression of a Respiratory Arsenate Reductase

2020 ◽  
Vol 86 (21) ◽  
Author(s):  
Dominik K. Haja ◽  
Chang-Hao Wu ◽  
Olena Ponomarenko ◽  
Farris L. Poole ◽  
Graham N. George ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Electron Acceptor ◽  
Specific Activity ◽  
Pyrococcus Furiosus ◽  
Arsenate Reductase ◽  
Pyrobaculum Aerophilum ◽  
Terminal Electron Acceptor ◽  
Content Type ◽  
Arsenic Tolerance

ABSTRACT Arsenate is a notorious toxicant that is known to disrupt multiple biochemical pathways. Many microorganisms have developed mechanisms to detoxify arsenate using the ArsC-type arsenate reductase, and some even use arsenate as a terminal electron acceptor for respiration involving arsenate respiratory reductase (Arr). ArsC-type reductases have been studied extensively, but the phylogenetically unrelated Arr system is less investigated and has not been characterized from Archaea. Here, we heterologously expressed the genes encoding Arr from the crenarchaeon Pyrobaculum aerophilum in the euryarchaeon Pyrococcus furiosus, both of which grow optimally near 100°C. Recombinant P. furiosus was grown on molybdenum (Mo)- or tungsten (W)-containing medium, and two types of recombinant Arr enzymes were purified, one containing Mo (Arr-Mo) and one containing W (Arr-W). Purified Arr-Mo had a 140-fold higher specific activity in arsenate [As(V)] reduction than Arr-W, and Arr-Mo also reduced arsenite [As(III)]. The P. furiosus strain expressing Arr-Mo (the Arr strain) was able to use arsenate as a terminal electron acceptor during growth on peptides. In addition, the Arr strain had increased tolerance compared to that of the parent strain to arsenate and also, surprisingly, to arsenite. Compared to the parent, the Arr strain accumulated intracellularly almost an order of magnitude more arsenic when cells were grown in the presence of arsenite. X-ray absorption spectroscopy (XAS) results suggest that the Arr strain of P. furiosus improves its tolerance to arsenite by increasing production of less-toxic arsenate and nontoxic methylated arsenicals compared to that by the parent. IMPORTANCE Arsenate respiratory reductases (Arr) are much less characterized than the detoxifying arsenate reductase system. The heterologous expression and characterization of an Arr from Pyrobaculum aerophilum in Pyrococcus furiosus provides new insights into the function of this enzyme. From in vivo studies, production of Arr not only enabled P. furiosus to use arsenate [As(V)] as a terminal electron acceptor, it also provided the organism with a higher resistance to arsenate and also, surprisingly, to arsenite [As(III)]. In contrast to the tungsten-containing oxidoreductase enzymes natively produced by P. furiosus, recombinant P. aerophilum Arr was much more active with molybdenum than with tungsten. It is also, to our knowledge, the only characterized Arr to be active with both molybdenum and tungsten in the active site.

scholarly journals Novel, Oxygen-Insensitive Group 5 [NiFe]-Hydrogenase in Ralstonia eutropha

2013 ◽  
Vol 79 (17) ◽  
pp. 5137-5145 ◽  
Author(s):  
Caspar Schäfer ◽  
Bärbel Friedrich ◽  
Oliver Lenz
Keyword(s):  
Biochemical Characterization ◽  
Ralstonia Eutropha ◽  
Specific Activity ◽  
Atmospheric Oxygen ◽  
Oxidation Activity ◽  
Tetrazolium Chloride ◽  
Content Type ◽  
Activity Measurements ◽  
Group 5

ABSTRACTRecently, a novel group of [NiFe]-hydrogenases has been defined that appear to have a great impact in the global hydrogen cycle. This so-called group 5 [NiFe]-hydrogenase is widespread in soil-living actinobacteria and can oxidize molecular hydrogen at atmospheric levels, which suggests a high affinity of the enzyme toward H2. Here, we provide a biochemical characterization of a group 5 hydrogenase from the betaproteobacteriumRalstonia eutrophaH16. The hydrogenase was designated an actinobacterial hydrogenase (AH) and is catalytically active, as shown by thein vivoH2uptake and by activity staining in native gels. However, the enzyme does not sustain autotrophic growth on H2. The AH was purified to homogeneity by affinity chromatography and consists of two subunits with molecular masses of 65 and 37 kDa. Among the electron acceptors tested, nitroblue tetrazolium chloride was reduced by the AH at highest rates. At 30°C and pH 8, the specific activity of the enzyme was 0.3 μmol of H2per min and mg of protein. However, an unexpectedly high Michaelis constant (Km) for H2of 3.6 ± 0.5 μM was determined, which is in contrast to the previously proposed lowKmof group 5 hydrogenases and makes atmospheric H2uptake byR. eutrophamost unlikely. Amperometric activity measurements revealed that the AH maintains full H2oxidation activity even at atmospheric oxygen concentrations, showing that the enzyme is insensitive toward O2.

Effects of the nitric oxide donor 3-morpholinosydnonimine (SIN-1) in focal cerebral ischemia dependent on intracellular brain pH

2002 ◽  
Vol 97 (4) ◽  
pp. 914-921 ◽  
Author(s):  
Bernard A. Coert ◽  
Robert E. Anderson ◽  
Fredric B. Meyer
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Nitric Oxide Donor ◽  
Protective Agent ◽  
No Donor ◽  
Content Type ◽  
Infarction Volume ◽  
Fine Print

Object. A nitric oxide (NO) donor that has been successfully used in the treatment of myocardial infarction, 3-morpholinosydnonimine (SIN-1), may be a potential neuroprotective agent. Production of NO in brain microsomes is dependent on the pH. The purpose of this study was to determine the efficacy of SIN-1 and its dependence on pH in vivo during periods of focal cerebral ischemia. Methods. At 0.1 or 1 mg/kg, SIN-1 was administered to 54 Wistar rats 30 minutes before a 2-hour period of focal cerebral ischemia under moderate hypo-, normo-, and hyperglycemic conditions. Measurements of brain intracellular pH (pHi); regional cortical blood flow, and the redox state of nicotinamide adenine dinucleotide were obtained in three additional animals to confirm the effects of the serum glucose manipulations. The animals were killed at 72 hours after the ischemic period to obtain infarction volumes. Administration of SIN-1 significantly reduced infarction in normoglycemic animals and, to a lesser extent, in hyperglycemic animals, indicating that SIN-1 was less effective under hyperglycemic conditions. At either dose SIN-1 had no significant effect on infarction volume in moderately hypoglycemic animals because moderate hypoglycemia in itself significantly (p < 0.005) reduced infarction volume. Conclusions. The NO donor SIN-1 may be a useful intraoperative cerebral protective agent. Furthermore, it is hypothesized that a mechanism that could explain the published discrepancies regarding the effects of NO donors in vivo may be affected by differences in ischemic brain acidosis.

Production of reactive oxygen species after reperfusion in vitro and in vivo: protective effect of nitric oxide

2000 ◽  
Vol 93 (1) ◽  
pp. 99-107 ◽  
Author(s):  
R. Bryan Mason ◽  
Ryszard M. Pluta ◽  
Stuart Walbridge ◽  
David A. Wink ◽  
Edward H. Oldfield ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Reperfusion Injury ◽  
Oxygen Free Radical ◽  
Content Type ◽  
Free Radical Production ◽  
Radical Production ◽  
Fine Print

Object. Thrombolytic treatments for ischemic stroke can restore circulation, but reperfusion injury, mediated by oxygen free radicals, can limit their utility. The authors hypothesized that, during reperfusion, nitric oxide (NO) provides cytoprotection against oxygen free radical species.Methods. Levels of NO and oxygen free radicals were determined in both reoxygenation in vitro and reperfusion in vivo models using an NO electrochemical probe and high-performance liquid chromatography with the 2,3- and 2,5-dihydroxybenzoic acid trapping method, before and after addition of the NO donor diethanolamine nitric oxide (DEA/NO).Reoxygenation after anoxia produced a twofold increase in NO release by human fetal astrocytes and cerebral endothelial cells (p < 0.005). In both cell lines, there was also a two- to threefold increase in oxygen free radical production (p < 0.005). In human fetal astrocytes and cerebral endothelial cells given a single dose of DEA/NO, free radical production dropped fivefold compared with peak ischemic levels (p < 0.001). In a study in which a rat global cerebral ischemia model was used, NO production in a vehicle-treated group increased 48 ± 16% above baseline levels after reperfusion. After intravenous DEA/NO infusion, NO reached 1.6 times the concentration of the postischemic peak in vehicle-treated animals. In vehicle-treated animals during reperfusion, free radical production increased 4.5-fold over basal levels (p < 0.01). After intravenous DEA/NO infusion, free radical production dropped nearly 10-fold compared with peak levels in vehicle-treated animals (p < 0.006). The infarct volume in the vehicle-treated animals was 111 ± 16.9 mm3; after DEA/NO infusion it was 64.8 ± 23.4 mm3 (p < 0.01).Conclusions. The beneficial effect of early restoration of cerebral circulation after cerebral ischemia is limited by reperfusion injury. These results indicate that NO release and oxygen free radical production increase during reperfusion, and suggest a possible early treatment of reperfusion injury using NO donors.

scholarly journals Transcriptomic Analysis of the Host Response to Giardia duodenalis Infection Reveals Redundant Mechanisms for Parasite Control

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Ernest A. Tako ◽  
Maryam F. Hassimi ◽  
Erqiu Li ◽  
Steven M. Singer
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Immune System ◽  
Immune Responses ◽  
Diarrheal Disease ◽  
Giardia Duodenalis ◽  
Parasite Control ◽  
Content Type ◽  
Deficient Mice

ABSTRACTThe immune system has numerous mechanisms that it can use to combat pathogens and eliminate infections. Nevertheless, studies of immune responses often focus on single pathways required for protective responses. We applied microarray analysis of RNA in order to investigate the types of immune responses produced against infection with the intestinal pathogenGiardia duodenalis. Infection withG. duodenalisis one of the most common causes of diarrheal disease in the world. While several potential antiparasitic effector mechanisms, including complement lysis, nitric oxide (NO), and α-defensin peptides, have been shown to inhibit parasite growth or killGiardia in vitro, studiesin vivohave thus far shown clear roles only for antibody and mast cell responses in parasite control. A total of 96 transcripts were identified as being upregulated or repressed more than 2-fold in the small intestine 10 days following infection. Microarray data were validated using quantitative PCR. The most abundant category of transcripts was antibody genes, while the most highly induced transcripts were all mast cell proteases. Among the other induced transcripts was matrix metalloprotease 7 (Mmp7), the protease responsible for production of mature α-defensins in mice. While infections in Mmp7-deficient mice showed only a small increase in parasite numbers, combined genetic deletion of Mmp7 and inducible nitric oxide synthase (iNOS, Nos2) or pharmacological blockade of iNOS in Mmp7-deficient mice resulted in significant increases in parasite loads following infection. Thus, α-defensins and NO are redundant mechanisms for control ofGiardiainfectionsin vivo.IMPORTANCEThe immune system has multiple weapons which it uses to help control infections. Many infections result in activation of several of these response mechanisms, but it is not always clear which responses actually contribute to control of the pathogen and which are bystander effects. This study used the intestinal parasiteGiardia duodenalisto examine the redundancy in immune responses during infections in mice. Our results showed that at least four distinct mechanisms are activated following infections. Furthermore, by blocking two pathways at the same time, we showed that both mechanisms contribute to control of the infection, whereas blocking single responses showed no or minimal effect in these cases.

Sign in / Sign up

Export Citation Format

Share Document