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Bacterial Invasion (bacterial + invasion)
Selected AbstractsBacterial invasion of dentinal tubules beneath apparently intact but hypomineralized enamel in molar teeth with molar incisor hypomineralizationINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 5 2008TOBIAS G. FAGRELL Background., The most common problems for a patient with molar incisor hypomineralization (MIH) are the collapse of enamel and cavitations, loss of fillings, and secondary caries, but most of all, severe hypersensitivity. Objective., The aim of this paper was therefore to histologically study possible bacterial invasion of dentinal tubules beneath apparently intact, but hypomineralized enamel in permanent molars with MIH. Material and methods., Five extracted permanent first molars diagnosed with MIH were fixated, demineralized, and sagittally serially sectioned in a bucco-lingual direction in a microtome with a thickness of 4,5 µm. Sections were stained with a modified Brown and Benn staining for bacteria, unstained sections were analysed in field emission SEM. Results., Stained sections from the cuspal areas, below the hypomineralized enamel, the staining indicated the presence of bacteria in the dentinal tubules. The HTX staining showed that the pulp in sections without any findings was normal and free from bacteria or infiltrates from inflammatory cells. In sections where bacteria were found in the cuspal areas or deeper in the dentin, a zone of reparative dentin was found, and in sections from one tooth, the coronal pulp showed an inflammatory reaction with inflammatory cells. In sections adjacent to those without any bacterial staining, the SEM analyses revealed empty dentinal tubules without any odontoblast processes or signs of bacteria. When odontoblast processes were found, the dentinal tubules were filled with bacteria located on the surface of the odontoblast processes. In some areas, a large number of tubules were found with bacteria. No bacteria were found close to the pulp. The odontoblast processes appeared larger in areas where bacteria were found. Conclusions., The presence of bacteria in the dentinal tubules and inflammatory reactions in the pulp indicate that oral bacteria may penetrate through the hypomineralized enamel into the dentin, thus possibly contribute to hypersensitivity of teeth with MIH. [source] Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat?FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Ēagla Tükel Abstract A massive neutrophil influx in the intestine is the histopathological hallmark of Salmonella enterica serovar Typhimurium-induced enterocolitis in humans. Two major hypotheses on the mechanism leading to neutrophil infiltration in the intestinal mucosa have emerged. One hypothesis suggests that S. enterica serovar Typhimurium takes an active role in triggering this host response by injecting proteins, termed effectors, into the host cell cytosol which induce a proinflammatory gene expression profile in the intestinal epithelium. The second hypothesis suggests a more passive role for the pathogen by proposing that bacterial invasion stimulates the innate pathways of inflammation because the pathogen-associated molecular patterns of S. enterica serovar Typhimurium are recognized by pathogen recognition receptors on cells in the lamina propria. A review of the current literature reveals that, while pathogen recognition receptors are clearly involved in eliciting neutrophil influx during S. enterica serovar Typhimurium infection, a direct contribution of effectors in triggering proinflammatory host cell responses cannot currently be ruled out. [source] Shigella spp. and enteroinvasive Escherichia coli pathogenicity factorsFEMS MICROBIOLOGY LETTERS, Issue 1 2005Claude Parsot Abstract Bacteria of Shigella spp. (S. boydii, S. dysenteriae, S. flexneri and S. sonnei) and enteroinvasive Escherichia coli (EIEC) are responsible for shigellosis in humans, a disease characterized by the destruction of the colonic mucosa that is induced upon bacterial invasion. Shigella spp. and EIEC strains contain a virulence plasmid of ,220 kb that encodes determinants for entry into epithelial cells and dissemination from cell to cell. This review presents the current model on mechanisms of invasion of the colonic epithelium by these bacteria and focuses on their pathogenicity factors, particularly the virulence plasmid-encoded type III secretion system. [source] The dietary histone deacetylase inhibitor sulforaphane induces human ,-defensin-2 in intestinal epithelial cellsIMMUNOLOGY, Issue 2 2008Markus Schwab Summary Antimicrobial peptides like human ,-defensin-2 (HBD-2) play an important role in the innate immune system protecting the intestinal mucosa against bacterial invasion. The dietary histone deacetylase (HDAC) inhibitors sulforaphane (SFN) and butyrate have received a great deal of attention because of their ability to simultaneously modulate multiple cellular targets involved in cellular protection. In this study the influence of SFN and butyrate on HBD-2 expression as well as the molecular pathways involved in SFN-mediated induction of HBD-2 were scrutinized. Treatment of Caco-2, HT-29 and SW480 cells with SFN led to a time- and dose-dependent upregulation of HBD-2 mRNA expression as determined by semi-quantitative reverse transcription,polymerase chain reaction. Moreover, HBD-2 protein production increased in response to SFN, measured by enzyme-linked immunosorbent assay. Induction of HBD-2 was also observed in response to butyrate. Immunofluorescence analysis revealed that the protein was localized in the cytosol. Coincubation of SFN with a vitamin D receptor (VDR), or an extracellular-regulated kinase 1/2 or a nuclear factor-,B inhibitor all reduced HBD-2 mRNA upregulation. In contrast, transfection of cells with a dominant-negative peroxisome proliferator-activated receptor , (PPAR,) mutant vector to inhibit PPAR, wild-type action and inhibition of p38 mitogen-activated protein kinase (MAPK) signalling did not affect SFN-mediated upregulation of HBD-2 mRNA. Moreover, SFN induced the expression of VDR, PPAR, and phosphorylated ERK1/2 but did not affect p38 MAPK activation. The data clearly demonstrate for the first time that the dietary HDAC inhibitor SFN is able to induce antimicrobial peptides in colonocytes. In this process HBD-2 expression is regulated via VDR, mitogen-activated protein kinase kinase/extracellular-regulated kinase and nuclear factor-,B signalling. [source] Inducible and constitutive ,-defensins are differentially expressed in Crohn's disease and ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 4 2003Jan Wehkamp Abstract Antimicrobial peptides such as defensins provide nonspecific mucosal defense against a multitude of microorganisms. Recently, it has been shown that luminal bacteria may invade the mucosa in inflammatory bowel diseases, suggesting a defect in innate mucosal immunity. The aim of this study was to investigate the expression of human ,-defensins (HBD) in controls, Crohn's disease (CD), ulcerative colitis (UC), and unspecific inflammation. Up to 4 biopsies were taken from 103 patients (33 controls, 24 with Crohn's disease, 36 with ulcerative colitis, 10 with unspecific colitis). Mucosal mRNA was measured using real-time fluorescence temperature cycler reverse-transcription polymerase chain reaction with primers for HBD-1, HBD-2, HBD-3, tumor necrosis factor ,, and interleukin 8. Mucosal HBD-1 expression was marginally decreased in both CD and UC. HBD-2 was increased exclusively in UC but not in CD. The expression of the novel defensin HBD-3 was strongly correlated with HBD-2 and also raised predominantly in UC. The expression of both inducible ,-defensins was enhanced in the state of inflammation. Expression of HBD-2 showed a weak correlation with interleukin 8 only in inflamed CD biopsies but not with tumor necrosis factor ,. The missing induction of both inducible ,-defensins in CD as compared with UC may cause a defect in barrier function that predisposes to bacterial invasion. [source] Hemin nutritional stress inhibits bacterial invasion of radicular dentine by two endodontic anaerobesINTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2007R. M. Love Abstract Aim, To determine if anaerobic bacteria routinely found in infected dentine and root canals require the presence of heme in the environment in order for them to invade dentinal tubules. Methodology, Noncarious, unrestored human teeth with single root canals were prepared for invasion experiments and soaked in either TSB-M supplemented with hemin (5 ,g mL,1) (n = 12 roots), TSB-M media (n = 12 roots) or TSB-M media followed by hemin soak (n = 12 roots) for 2 days, then inoculated with either Prevotella intermedia ATCC 25611 or Peptostreptococcus micros ATCC 33270 and incubated anaerobically for 14 days. Roots were prepared for light microscopy, stained with Brown and Brenn or antisera raised to the bacteria, and invasion within tubules assessed using a tubule invasion index (TI). Data were analysed using Student's t -test and Mann,Whitney U -test. Results,Prevotella intermedia (TI = 0.7 ± 0.04) and P. micros (TI = 0.96 ± 0.08) showed low invasion when grown in the presence of hemin with cells generally restricted to the superficial 20 ,m of the tubules, whilst neither bacteria invaded tubules (TI = 0) when hemin was absent from the growth media (P < 0.01). Conclusions, Hemin was required in the growth medium for P. intermedia and P. micros to invade dentinal tubules. [source] Bacterial invasion of dentinal tubules beneath apparently intact but hypomineralized enamel in molar teeth with molar incisor hypomineralizationINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 5 2008TOBIAS G. FAGRELL Background., The most common problems for a patient with molar incisor hypomineralization (MIH) are the collapse of enamel and cavitations, loss of fillings, and secondary caries, but most of all, severe hypersensitivity. Objective., The aim of this paper was therefore to histologically study possible bacterial invasion of dentinal tubules beneath apparently intact, but hypomineralized enamel in permanent molars with MIH. Material and methods., Five extracted permanent first molars diagnosed with MIH were fixated, demineralized, and sagittally serially sectioned in a bucco-lingual direction in a microtome with a thickness of 4,5 µm. Sections were stained with a modified Brown and Benn staining for bacteria, unstained sections were analysed in field emission SEM. Results., Stained sections from the cuspal areas, below the hypomineralized enamel, the staining indicated the presence of bacteria in the dentinal tubules. The HTX staining showed that the pulp in sections without any findings was normal and free from bacteria or infiltrates from inflammatory cells. In sections where bacteria were found in the cuspal areas or deeper in the dentin, a zone of reparative dentin was found, and in sections from one tooth, the coronal pulp showed an inflammatory reaction with inflammatory cells. In sections adjacent to those without any bacterial staining, the SEM analyses revealed empty dentinal tubules without any odontoblast processes or signs of bacteria. When odontoblast processes were found, the dentinal tubules were filled with bacteria located on the surface of the odontoblast processes. In some areas, a large number of tubules were found with bacteria. No bacteria were found close to the pulp. The odontoblast processes appeared larger in areas where bacteria were found. Conclusions., The presence of bacteria in the dentinal tubules and inflammatory reactions in the pulp indicate that oral bacteria may penetrate through the hypomineralized enamel into the dentin, thus possibly contribute to hypersensitivity of teeth with MIH. [source] Signal transduction and functional changes in neutrophils with agingAGING CELL, Issue 4 2004Tamas Fulop Summary It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age. [source] Evidence of enhanced bacterial invasion during Diplostomum spathaceum infection in European grayling, Thymallus thymallus (L.)JOURNAL OF FISH DISEASES, Issue 2 2006P Pylkkö Abstract Farmed grayling, Thymallus thymallus (L.), are susceptible to atypical Aeromonas salmonicida (aAS) infections. Interactions between bacteria and parasites were studied using grayling subjected to concomitant exposure to aAS bacteria and the digenean parasite Diplostomum spathaceum. Atypical AS was detected from fish by a combination of bacterial cultivation and polymerase chain reaction techniques. A detection level of 17 aAS cells per 100 mg intestine tissue sample was obtained. Concomitant bacterial exposure did not enhance the severity of grayling eye rupture and nuclear extrusion induced by D. spathaceum, but D. spathaceum invasion into grayling increased the proportion of fish carrying aAS in their heart tissue. However, the number of aAS cells detected in heart tissue was low. Atypical AS did not cause acute disease or mortality during 15 days post-exposure. There was a higher prevalence of aAS in grayling heart samples than in intestinal samples, indicating that the intestine is not favoured by aAS. We suggest that heart tissue would be a good organ from which to isolate aAS when tracing latent carrier fish. We conclude that penetrating diplostomids can enhance bacterial infections in fish and that diplostomids can cause serious eye ruptures in grayling. [source] A Raman spectroscopic and combined analytical approach to the restoration of severely damaged frescoes: the Palomino projectJOURNAL OF RAMAN SPECTROSCOPY, Issue 4 2008Howell G. M. Edwards Abstract The deterioration of art objects is normally relatively minor, controllable and attributable to environmental changes or bacterial invasion, and until now there has not been any recorded attempt to analyse an artwork that has been deliberately and significantly destroyed. The analytical problems are correspondingly larger but the potential reward from any information that can be forthcoming is thereby proportionately greater. The 17th Century Palomino frescoes on the vaulted ceiling of the Church of Sant Joan del Mercat in Valencia were largely destroyed by insurgents in the Spanish Civil War in 1936. The ensuing gunfire and a series of seven conflagrations inside the church had a devastating effect upon the artwork, and the surviving areas were also rendered unstable with respect to their detachment from the substrate. During the current restoration project being undertaken on these frescoes, an opportunity was provided for the application of several analytical techniques to secure information about the original pigment palette employed, the technology of application used by Palomino and the changes consequent upon the destruction process. Here, we report for the first time the use of analytical Raman spectroscopy, supported by scanning electron microscopy (SEM) and voltammetry of microparticles, for the combined identification of pigments, binders, substrate treatments and pigment alteration in an important, although badly damaged, wall painting for the informing of the ongoing conservation and restoration strategy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Bacterial chemoattraction towards jasmonate plays a role in the entry of Dickeya dadantii through wounded tissuesMOLECULAR MICROBIOLOGY, Issue 3 2009Maria Antunez-Lamas Summary Jasmonate is a key signalling compound in plant defence that is synthesized in wounded tissues. In this work, we have found that this molecule is also a strong chemoattractant for the phythopathogenic bacteria Dickeya dadantii (ex- Erwinia chysanthemi). Jasmonic acid induced the expression of a subset of bacterial genes possibly involved in virulence/survival in the plant apoplast and bacterial cells pre-treated with jasmonate showed increased virulence in chicory and Saintpaulia leaves. We also showed that tissue wounding induced bacterial spread through the leaf surface. Moreover, the jasmonate-deficient aos1 Arabidopsis thaliana mutant was more resistant to bacterial invasion by D. dadantii than wild-type plants. These results are consistent with the hypothesis that sensing jasmonic acid by this bacterium helps the pathogen to ingress inside plant tissues. [source] Presence of Subepithelial Lymphoid Nodules in the Teat of EwesANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2007V. S. Mavrogianni Summary A total of 87 clinically healthy ovine teats were examined bacteriologically (by scraping the mucosa) and histologically. Teats examined were those of lactating mammary glands with no bacteria isolated (n = 23); of mammary glands after cessation of lactation with no bacteria isolated (n = 25); of lactating mammary glands with bacteria isolated (n = 22); and of mammary glands after cessation of lactation with bacteria isolated (n = 17). The salient histological feature was subepithelial leucocytic infiltration. In teat cisterns, lymphocytes were the predominant cell type and in teat ducts, lymphocytes and neutrophils were seen in equal proportions. Subepithelial lymphoid nodules, some with germinal centres, were detected in 43 (49%) teats. The majority of lymphoid nodules was observed at the border between teat duct and teat cistern. Presence of bacteria was significantly associated with the presence of leucocytic activity (P < 0.001) and with the presence of lymphoid nodules (P = 0.032). We conclude that the presence of induced subepithelial lymphoid tissue at the border between teat duct and teat cistern appears to be important in protecting the mammary gland during the early stages of bacterial invasion. The findings call for further investigations into the lymphoid structures of the teat; these should elucidate the role and development of mammary mucosa-associated lymphoid tissues and may lead to strategies for enhancing non-specific defence mechanisms of the mammary gland. [source] Octopamine and 5-hydroxytryptamine mediate hemocytic phagocytosis and nodule formation via eicosanoids in the beet armyworm, Spodoptera exiguaARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2009Geun Seob Kim Abstract Octopamine and 5-hydroxytryptamine (5-HT) have been known to mediate cellular immune responses, such as hemocytic phagocytosis and nodule formation, during bacterial invasion in some insects. In addition, eicosanoids also mediate these cellular immune reactions in various insects, resulting in clearing the bacteria circulating in the hemolymph. This study investigated a hypothesis on signal cross-talk between both types of immune mediators in the beet armyworm, Spodoptera exigua, which had been observed in the effect of eicosanoids on mediating the cellular immune responses. In response to bacterial infection, octopamine or 5-HT markedly enhanced both hemocytic phagocytosis and nodule formation in S. exigua larvae. Their specific antagonists, phentolamine (an octopamine antagonist) or ketanserin (a 5-HT antagonist) suppressed both cellular immune responses of S. exigua. These effects of biogenic monoamines on the immune mediation were expressed through eicosanoids because the inhibitory effects of both antagonists were rescued by the addition of arachidonic acid (a precursor of eicosanoid biosynthesis). Furthermore, the stimulatory effects of both monoamines on the cellular immune responses were significantly suppressed by different inhibitors acting at their specific levels of eicosanoid biosynthesis. Taken together, this study suggests that octopamine and 5-HT can mediate hemocytic phagocytosis and nodule formation through a downstream signal pathway relayed by eicosanoids in S. exigua. © 2009 Wiley Periodicals, Inc. [source] Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitroCELLULAR MICROBIOLOGY, Issue 2 2009Tobias Tenenbaum Summary Previous experimental studies in a standard Transwell culture system have shown Streptococcus suis ability to compromise barrier function of porcine choroid plexus epithelial cells (PCPEC). The development of an ,inverted' Transwell filter system of PCPEC enables us now for the first time to investigate bacterial invasion and translocation from the physiologically relevant basolateral (blood) to the apical (cerobrospinal fluid) side. Most importantly, we observed specific invasion and translocation of S. suis across the PCPEC exclusively from the basolateral side. During this process, bacterial viability and the presence of a capsule as well as cytoskeletal regulation of PCPEC seemed to play an important role. No loss of barrier function was observed. Bacterial translocation could be significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002, but not by its inactive analogue Ly303511 or dexamethasone. Apotome imaging as well as electron microscopy revealed intracellular bacteria often in cell vacuoles. Thus, possibly regulated by the presence of a capsule, S. suis induces signals that depend on the lipid kinase phosphatidylinositol 3-kinase pathway, which paves the way for cellular uptake during the bacterial transcellular translocation process. Taken together, our data underline the relevance of the blood,cerebrospinal fluid barrier as a gate for bacterial entry into the central nervous system. [source] Listeria monocytogenes -infected bone marrow myeloid cells promote bacterial invasion of the central nervous systemCELLULAR MICROBIOLOGY, Issue 2 2005Olivier F. Join-Lambert Summary Listeria monocytogenes is a facultative intracellular pathogen that is able to invade the central nervous system causing meningoencephalitis and brain abscesses. The mechanisms allowing bacteria to cross the blood,brain barrier are poorly understood. In this work, we used an experimental model of acute listeriosis in the mouse inducing a reproducible invasion of the central nervous system. At the early phase of infection, we find that bacteria invade and rapidly grow in bone marrow cells identified as bone marrow myelomonocytic cells expressing the phenotype CD31pos:Ly-6Cpos:CD11bpos:LY-6Glow. We demonstrate that central nervous system invasion is facilitated by injecting L. monocytogenes- infected bone marrow cells in comparison with free bacteria or infected spleen cells. In mice transplanted with bone marrow cells from transgenic donor mice expressing the green fluorescent protein (GFP), we show that infected myeloid GFP+ cells adhere to activated brain endothelial cells, accumulate in brain vessels and participate to the pathogenesis of meningoencephalitis and brain abscesses. Our results demonstrate that bone marrow, the main haematopoietic tissue, is a previously unrecognized reservoir of L. monocytogenes -infected myeloid cells, which can play a crucial role in the pathophysiology of meningoencephalitis by releasing infected cells into the circulation that ultimately invade the central nervous system. [source] Functions and effectors of the Salmonella pathogenicity island 2 type III secretion systemCELLULAR MICROBIOLOGY, Issue 8 2003Scott R. Waterman Summary Salmonella enterica uses two functionally distinct type III secretion systems encoded on the pathogenicity islands SPI-1 and SPI-2 to transfer effector proteins into host cells. A major function of the SPI-1 secretion system is to enable bacterial invasion of epithelial cells and the principal role of SPI-2 is to facilitate the replication of intracellular bacteria within membrane-bound Salmonella -containing vacuoles (SCVs). Studies of mutant bacteria defective for SPI-2-dependent secretion have revealed a variety of functions that can be attributed to this secretion system. These include an inhibition of various aspects of endocytic trafficking, an avoidance of NADPH oxidase-dependent killing, the induction of a delayed apoptosis-like host cell death, the control of SCV membrane dynamics, the assembly of a meshwork of F-actin around the SCV, an accumulation of cholesterol around the SCV and interference with the localization of inducible nitric oxide synthase to the SCV. Several effector proteins that are translocated across the vacuolar membrane in a SPI-2-dependent manner have now been identified. These are encoded both within and outside SPI-2. The characteristics of these effectors, and their relationship to the physiological functions listed above, are the subject of this review. The emerging picture is of a multifunctional system, whose activities are explained in part by effectors that control interactions between the SCV and intracellular membrane compartments. [source] Interaction of cblA/adhesin-positive Burkholderia cepacia with squamous epitheliumCELLULAR MICROBIOLOGY, Issue 2 2002Umadevi Sajjan Summary A highly transmissible strain of Burkholderia cepacia from genomovar III carries the cable pilin gene, expresses the 22 kDa adhesin (cblA+ve/Adh +ve), binds to cytokeratin 13 (CK13) and is invasive. CK13 is expressed abundantly in the airway epithelia of cystic fibrosis (CF) patients. We have now investigated whether binding of cblA+ve/Adh +ve B. cepacia to CK13 potentiates bacterial invasion and epithelial damage using bronchial epithelial cell cultures differentiated into either squamous (CK13-enriched) or mucociliary (CK13-deficient) epithelia. Three different B. cepacia isolates (cblA+ve/Adh +ve, cblA+ve/Adh ,ve and cblA,ve/Adh ,ve) showed minimal binding to mucociliary cultures, and did not invade or cause cell damage. In contrast, the cblA+ve/Adh +ve isolate, but not others, bound to CK13-expressing cells in squamous cultures, caused cytotoxicity and stimulated IL-8 release within 2 h. By 24 h, this isolate invaded and migrated across the squamous culture, causing moderate to severe epithelial damage. A specific antiadhesin antibody, which blocked the initial binding of the cblA+ve/Adh +ve isolate to CK13, significantly inhibited all the pathologic effects. Transmission electron microscopy of squamous cultures incubated with the cblA+ve/Adh +ve isolate, revealed bacteria on the surface surrounded by filopodia by 2 h, and within the cells in membrane-bound vesicles by 24 h. Bacteria were also observed free in the cytoplasm, surrounded by intermediate filaments containing CK13. These findings suggest that binding of B. cepacia to CK13 is an important initial event and that it promotes bacterial invasion and epithelial damage. [source] Early-onset Group B streptococcal sepsis in a preterm infant with Kostmann syndromeACTA PAEDIATRICA, Issue 12 2002T Fujiu A preterm infant died of group B streptococcal sepsis 7 h after birth. The infant's complete blood count showed total agranulocytosis. Histopathology of the major organs showed significant bacterial invasion without infiltration of polymorphonuclear leucocytes. Examination of the bone marrow revealed normal cellularity of the granulocyte precursors with arrested maturation. These findings are consistent with Kostmann syndrome. Conclusion: It is suggested that in patients with deteriorating early-onset infection, underlying congenital abnormalities in host defence, such as Kostmann syndrome, should be considered. [source] | ||||||||||||||||