Candida albicans was the predominant yeast isolated [30 patients (62.5%)], followed by C. parapsilosis [6 (12.5%)] and C. dubliniensis 5 (10.4%). Aspergillus fumigatus was the most common filamentous fungus [5 (10.4%)] and non-fumigatus Aspergillus species were isolated from four (8.3%) patients. Staphylococcus aureus was the most frequently detected bacterium in C. check details albicans

positive samples (53.57%). A. fumigatus and Pseudomonas aeruginosa or S. aureus were detected together in 75% of A. fumigatus positive samples each. No statistically significant relationship was detected between growth of yeast and moulds and age, gender, the use of inhaled corticosteroids or tobramycin. No significant correlation was found between the isolation of C. albicans, A. fumigatus and P. aeruginosa, Stenotrophomonas maltophilia PLX4032 price or S. aureus, and the isolation of C. albicans and Haemophilus influenzae. Other factors which may be responsible for the increased isolation of fungi in CF need to be investigated. “
“Patients with acute myelogenous leukaemia (AML) and neutropenia after chemotherapy are at high risk for life-threatening invasive fungal disease (IFD), in particular, invasive aspergillosis (IA). The aim of the study was to evaluate data on characteristics, risk factors, complications and additional

antifungal treatment of patients with AML receiving posaconazole prophylaxis (PP) after chemotherapy in an actual clinical setting. A retrospective single-centre observational study on 40 patients with AML, median age 66 years, was conducted. PP 200 mg three times daily was given routinely. After 76 cycles of remission induction chemotherapy followed by PP, median duration of 31 days (range 6–61 days), no fatal case occurred. Hydroxychloroquine The majority of patients had at least one additional risk factor for IFD and during 32 cycles (42.1%), three risk factors were present. During 40 therapy cycles (52.6%), fever of unknown origin occurred. Pneumonia was diagnosed after 23 cycles

(30.3%), thereof one case of proven IA (1.3%). PP was interrupted in 25 cycles (32.9%) and was followed by systemic antifungal therapy with different agents, with a median duration 15 days (range: 6–32 days). PP appears to be an effective and well-tolerated protection against IFD for AML patients under natural clinical conditions. “
“Data on the epidemiology of invasive Candida infections in paediatric patients in Europe are still limited. The aim of this retrospective study was to analyse the epidemiology of candidaemia in a tertiary paediatric hospital in Poland from 2000 to 2010. Using microbiological records, a total of 118 episodes of candidaemia were identified in 114 children, with an annual incidence of 0.35 episodes/1000 discharges. The highest incidences were found in the medical intensive care unit (5.28), and in neonatal intensive care (1.47). The mortality rate was 8.5%. Candida albicans and C. parapsilosis were the most prevalent species (39.8% and 35.6% respectively).

[25] The CRTH2 agonist activity of Pyl A was confirmed with a gold standard experiment based on the work of Cossette, Monneret and Nagata, in which the CRTH2 agonists PGD2, DK-PGD2, indomethacin and 15dPGJ2 cause up-regulation of CR3 (CD11b) in granulocytes.[15, 27, 30-32] Pyl

A caused a significant increase in the expression of CR3 (CD11b) in human eosinophils, which could be attenuated by pre-incubation with the CRTH2 antagonist GSKCRTH2X (Fig. 2), further confirming activity at the CRTH2 receptor. CR3 (CD11b) up-regulation via CRTH2 is believed to aid cell adhesion to the vascular wall for migration of cells from the blood into tissue at sites of inflammation.[33] The murine CRTH2 gene was first cloned and characterized by Abe et al.[34] and shares 77% homology with the

human CRTH2 receptor gene. Selleckchem MLN2238 The pharmacologies of the human and mouse CRTH2 receptors are virtually identical, and the receptors share 90% homology within the transmembrane domains.[35] The CRTH2 agonists PGD2, DK-PGD2, 15dPGJ2 and indomethacin all show activity to the mouse CRTH2 receptor.[36-39] 15dPGJ2 binds to the mouse CRTH2 receptor with an affinity several orders of magnitude greater than that seen for peroxisome proliferator-activated Fer-1 mw receptor-γ.[39, 40] We detected CRTH2 mRNA in the mouse myometrium using the primers used by Abe et al.,[34] (Fig. 1). There was no difference in mRNA expression between vehicle and Pyl A-treated or LPS-treated mice and LPS/Pyl A-treated mice. However, the degree of expression seen at the mRNA level suggests that CRTH2 is expressed in the myometrium. Determining if expression is seen on both myocytes and infiltrating leucocytes or leucocytes alone has not been possible because of the lack of available specific antibodies to murine CRTH2. Human studies have demonstrated mRNA expression in the myometrium,

but flow cytometry confirms the absence of the expressed protein in cultured myocytes.[41] CRTH2 positive leucocytes are also detected in the endometrium and are likely Meloxicam to be recruited to decidua via PGD2.[42, 43] We have previously reported that the CRTH2 agonist 15dPGJ2 delays LPS-induced preterm labour in the mouse, which is thought to be via NF-κB inhibition in the myometrium.[13] 15dPGJ2 also inhibits NF-κB in human cultured amniocytes and myocytes;[12] however, the mechanism by which NF-κB inhibition is achieved is unclear. It was therefore hypothesized that Pyl A could reproduce the effects of 15dPGJ2 of delaying preterm labour by diminishing the pro-inflammatory effect of LPS via NF-κB inhibition. However, co-injection of LPS-treated mice with Pyl A was found to exacerbate time to preterm labour in a dose-dependent response (Fig. 4b).

While results in the laboratory have shown great potential for MSC to exert immunomodulatory effects and promote regeneration and repair following disease, it should not be ignored that some studies have demonstrated that the therapeutic effect of MSC can vary.66,76 In steady state, intravenously injected MSC migrate to the BM.77,78 In the setting of inflammatory damage, MSC preferentially home to the site of inflammation where they then migrate across the endothelium and enter the injured organ,46,56,79–81 to some extent analogous to leukocyte trafficking (Fig. 2). The in vivo tracking of fluorescently labelled

MAPK Inhibitor Library mw MSC have demonstrated that these cells infiltrate the peritubular capillaries and glomeruli of kidneys with IR injury within 10 min of injection, with no cells evident by 72 h.62 The precise mechanisms of MSC homing to sites of tissue injury are not fully understood. However, Bi et al.57 reported that the beneficial effects of administering MSC to mice with cisplatin-induced injury were also observed when MSC-conditioned media was administered without the cells. This implies that the mechanisms in which MSC

confer protection Everolimus is not entirely attributed to their ability to home and engraft to the site of kidney damage. The study highlights that MSC are also capable of mediating protection via an endocrine manner.57 Mesenchymal stem cells have numerous chemokine receptors that may assist in their migration to sites of inflammation.82,83 Carnitine dehydrogenase Following ischemic injury, the expression of the chemokine stromal cell-derived factor-1 (SDF-1), also known as CXCL12, is upregulated within the kidney.84 MSC express the

SDF-1 receptor CXCR4, which is further upregulated under hypoxic conditions.85,86 In addition, when MSC are pre-incubated with TNF-α they show an increased migratory capacity towards SDF-1 indicating that a SDF-1/CXCR4 interaction may mediate the localization of exogenously injected MSC to sites of tissue injury.87,88 Ponte et al.88 tested the ability of MSC to home towards 16 different growth factors and chemokines in vitro and found that platelet-derived growth factor-AB (PDGF-AB) and IGF-1 were the most potent chemoattractants for MSC. CD44 is another candidate that has been shown to play a vital role in MSC trafficking.56,89 CD44 on MSC binds to hyaluronic acid (HA), which is significantly upregulated in the kidney following ischemic injury.56,90 Supportive studies by Herrera et al.56 show that the injection of either MSC derived from CD44 null mice, or MSC incubated with a CD44 blocking antibody or soluble HA, did not migrate to the kidney following glycerol induced damage. However, MSC homing was restored when these CD44-negative cells were transfected with wild-type CD44, indicating that CD44/HA interactions are required for the migration of MSC to the kidney following injury.

TAMs in the colorectal cancer model were also found to produce chemokines that attract T cells (Fig. 3B and C). The attraction of T cells is particularly important PF-02341066 cell line since T cells are known to be the major effectors in anti-tumour immune responses 11, 13. Amongst these chemokines, CXCL9 and CXCL10, both IFN-γ inducible chemokines, are strong chemoattractants for TH1 cells 26. TH1 cells are important for promoting the killing of tumour cells by cytotoxic T cells 27, 28, and the presence of TH1 cells in colorectal tumours has been correlated with good clinical outcome 11. In addition, TAMs isolated from the co-culture spheroids were capable of stimulating allogeneic T-cell proliferation and activating type-1

T cells (Fig. 4). Taken together, the data suggest that TAMs in colorectal cancers create a type-1 inflammatory microenvironment. These new findings establish the link between clinical observations where (i) a high macrophage infiltration and

(ii) a type-1 adaptive immunity in human colorectal tumours independently have been correlated with beneficial clinical outcomes Napabucasin purchase 11, 29. Importantly, the in vitro findings were also observed in primary colorectal tumour tissues (Figs. 5 and 6). TAMs in vivo were pro-inflammatory, the number of tumour-infiltrating T cells correlated well with the number of TAMs and T cells of the type-1 inflammatory phenotype were present. Notably, the two patients with metastasis of the primary colorectal tumour (25271 and 25316) had the lowest TAM (23–35 TAMs per FOV) and T-cell infiltration (37–55 T cells per FOV, Table 1). Amongst these two patients, the one who Endonuclease had more metastasis and did not survive beyond 5 years (25316) had a lower percentage of IFN-γ-positive TAMs (6.6%) and T cells (45%). This supports our hypothesis that the attraction and activation of type-1 T cells into the tumour by pro-inflammatory TAMs play a crucial role in suppressing tumour progression.

For the first time, we have dissected the potential tumour-suppressive roles of TAMs in human colorectal tumours. The data suggest that in vivo, pro-inflammatory TAMs recruit T cells to the tumour site, present antigens and provide co-stimulating signals to activate the T cells, and subsequently promote the type-1 inflammatory response that leads to downstream anti-tumour immune activities. These findings explain the observation that high macrophage infiltration into colorectal cancers correlates with good patient prognoses. Besides helping us to understand how TAMs execute their tumour-suppressive role, these novel findings will contribute towards the rational design of therapeutic strategies to harness the power of TAMs for cancer treatment in future. It is noteworthy that the tumour types in which TAMs have been observed to exert a tumour-suppressive effect are located in the barrier organs of the body, namely the colon, stomach and skin.

Furthermore,

a Cbl-b-MyD88 regulatory axis is not required for TLR inhibition in macrophages. Instead, Itgb2−/- macrophages presented with enhanced IκBα degradation, leading to changes in NF-κB recruitment to target promoters and elevated cytokine, chemokine, and anti-apoptotic gene transcription. Thus, β2 integrins limit TLR signaling by inhibiting NF-κB pathway activation and promoting p38 MAPK activation, thereby fine-tuning TLR-induced inflammatory responses. Innate immune cell activation depends on the activity of Toll-like receptors (TLRs) that bind conserved molecular features expressed on invading pathogens [1]. Upon encountering microbes, macrophages and dendritic cells (DCs) respond to TLR stimulation by inducing antimicrobial and antiviral programs that result in the rapid synthesis and secretion Ruxolitinib of inflammatory cytokines and type I interferons. In turn, this potent response must be restrained to spare host tissues from the deleterious effects of exaggerated inflammation. This is accomplished by a variety of inhibitory mechanisms, including cytoplasmic effectors that block TLR signaling directly as well as secreted negative regulators, which work together to limit the severity of the immune response [2]. Although originally considered as an archetypal cell activation pathway, signals through immunoreceptor tyrosine-based

activation motifs (ITAMs) display functional heterogeneity and have been PF-2341066 recently appreciated to cross-inhibit TLR responses [3, 4]. ITAM signaling in myeloid cells is mediated by the ITAM-containing molecules DAP12 and FcRγ, which act as signaling adapters for an extensive collection of cell surface receptors [5-7]. Following ligand binding by paired receptors, ITAM signaling via DAP12 and FcRγ in myeloid cells proximally activates

Src-family kinases and Syk kinase to enable downstream signals that are predominantly associated with cellular activation, including inducing NF-κB and MAPK pathways, and prompting the release of intracellular oxyclozanide Ca2+ stores [5]. However, depending on the identity of the associated receptor and other undefined parameters, ITAM-based signaling can also induce inhibitory responses. For example, triggering of the DAP12-coupled TREM-2 receptor can dampen TLR activation in macrophages [8]. In addition, TREM-2 and/or DAP12-deficient macrophages and DCs produce more inflammatory cytokines in response to TLR stimulation [9-12], demonstrating that these adapter molecules can transduce signals attenuating TLR activation. During an inflammatory response, leukocytes in the blood adhere to the activated vascular endothelium through the use of integrins. In particular, members of the β2 integrin family facilitate leukocyte firm adhesion, thereby allowing for cell extravasation into the tissues [13].

This suggests that while cells may adopt more than one phenotype, they do not necessarily coproduce more than one signature cytokine in vivo at any single point in time. Because of the quite extensive cross-regulation between these phenotypes, it remains most likely that phenotype induction of individual cells depends on the status of other cells in the same microenvironment. Future work will reveal which phenotypes are

‘compatible’ for co-expression in single Th cells and which ones are not. Although helper T-cell responses are generally referred to as a single entity, Th responses are made up of thousands to millions of cells. High-throughput technologies such as mRNA profiling and ChIP-seq are however unable to delineate find more the heterogeneity within these cell populations. New techniques now allow detailed mapping of per-cell movement in vivo with real-time imaging [87, 88]. Each tracked cell differentiates and makes a phenotype choice. Given that the number of molecules involved is very small, stochasticity plays a large role in determining the outcome of the phenotype choice, which means that cells adopting the opposite phenotype

are inevitable [89-91]. Mathematical models have been used to study the role of stochasticity in the context of Th-cell differentiation and have for instance shown that even in a strongly Th2-skewing environment, some cells will adopt an alternative click here phenotype [73]. Further variation comes from the cell’s microenvironment where local fluctuations in cytokines may deviate from the global concentrations in the tissue, leading to Th cells adopting alternative phenotypes [92]. Every response is therefore heterogeneous at the single until cell level, due to chance events at the single cell level. However, at the population level, the variability evens out due to the large number of cells that respond. This makes predicting behaviour of the population

possible, even though the individual cells display stochastic behaviour [93-95]. Although the decisions made by individual Th cells responding to antigen can be seen as independent chance events, they are affected by similar choice events in their local neighbourhood. Th cells have been shown to have effects on a spatial scale that is slightly larger than their immediate neighbourhood [96]. Cells can therefore be affected by neighbouring Th cells and be induced to change phenotype at an early stage after the initial decision. In this way, all cells in the same local microenvironment should come to a consensus by overruling Th cells that by chance are adopting a discordant phenotype. Such a local quorum sensing would resolve most of the inherent uncertainty in the decision-making process [97, 98]. In that sense, the local cytokine environment dampens the stochastic choices that individual cells make.

bakeri by passage in naïve and immune hosts (131–133). Murine host resistance is linked to genes located both within and outside of the MHC (132). Selection in immune hosts tends to reduce the immunogenicity Bortezomib supplier of the parasite, as measured by eosinophilia, lymphocytosis in the spleen and regional lymph nodes and antibody response (131). We have found that H. bakeri establishes long-term primary infections of at least 120 days duration in CBA/Ca and BALB/c mice (76,77). Host resistance in primary infections is not enhanced by overexpression of IL-5(76), and conversely, the intensity of infection is not enhanced by deletion of IL-5 (69) or eotaxin (76). Although an eosinophilic inflammatory response surrounds

larvae embedded in the duodenal wall and irradiated larvae appear to induce resistance at this stage of infection, these results suggest that eosinophils play little role in protecting against this parasite. Wild-type FVB/N mice, which are highly resistant to N. brasiliensis, most likely in the pre-lung phase, are no more resistant to H. bakeri than WT CBA/Ca mice (77). Our studies with H. bakeri were terminated after more than 4 months, when egg production in WT, eotaxin−/− and STAT6−/− mice was 50–100% of that seen in the first three

weeks of infection (76), so we have yet to determine whether expulsion is affected by the deletion of these genes. H. bakeri is generally considered to be capable of inducing strong immunosuppression (134–136) acetylcholine and so deletion of eotaxin or STAT6 may have little additional impact. As a parasite largely restricted to the gut, it is also unlikely to be SRT1720 exposed to the same array of mechanisms that protect against N. brasiliensis and S. ratti. T. canis elicits strong peripheral blood eosinophilia and eosinophil-rich granulomas can surround larvae. Although anti-IL-5 antibody treatment can suppress eosinophilia in mice infected with T. canis, it does not increase larval load in the liver (137), an observation supported by the observation that IL-5−/− mice are no more susceptible to T. canis than WT controls (138). In conjunction with Jim Parsons (Victorian Institute of Animal Science), we have shown that

in IL-5 Tg mice infected with T. canis, the numbers of larvae recovered from liver, brain and muscle are comparable to those in WT littermates (64). It would seem then that T. canis is neither enhanced nor disadvantaged by eosinophilia and larvae are resistant to damage and killing by eosinophils, though these cells may contribute to lung pathology (138). Eosinophilia is suppressed in T. canis-infected pregnant and lactating dogs and this may allow larvae to escape granulomas, thereby facilitating transmission to offspring. Although T. canis does not suppress eosinophilia in our murine models, excretory-secretory proteins released from T. canis larvae in vitro do impact on eosinophil behaviour and protective innate anti-nematode resistance (139).

We found that both T conventional (Tconv; defined as FACS-sorted CD4+CD25−) and Tregs produced CXCL8 at similar concentrations (Fig. 1B and C) even in the absence

of TCR activation, suggesting that like endothelial cells, T cells may have preformed stores of CXCL8 15 that are released upon the shear stress of cell sorting. Notably, CXCL8 production by CD25− and CD25hi T cells was not restricted to cells with a naïve (CD45RA+) or memory (CD45RA−) phenotype. Similar results were obtained when cells were stimulated in the presence of exogenous IL-2 (data not shown). In parallel, we analyzed production of IFN-γ or IL-17 and confirmed that the CD25hiCD45RA− Tregs produce a significant amount of IL-17, and that neither CD25hiCD45RA− nor CD25hiCD45RA+ Tregs produced IFN-γ (Fig. 1B). These findings indicate that CD4+CD25hi Tregs produce CXCL8 irrespective of whether they are naïve or memory https://www.selleckchem.com/products/RO4929097.html cells and that this finding is not the result of contaminating IL-17-secreting cells. Isolation of cells on the basis of CD25, even in conjunction with other markers such as CD45, does not necessarily result in a homogeneous population of FOXP3+ cells. Therefore, to further confirm

that Tregs produce this chemokine, CXCL8 production was analyzed by intracellular staining. Ex vivo CD4+ T cells were stimulated with PMA/ionomycin for 6 h and CXCL8 producing cells were detected in both the FOXP3+ and FOXP3− populations (Fig. 1D and E). On average, 28.1%±1.0 (n=4, average±SEM) of stimulated CD4+FOXP3− T cells and 25.3%±4.1 (n=4) of stimulated CD4+FOXP3+ T cells were CXCL8+ (Fig. LEE011 1E). To further confirm these data, as well as to determine the cytokine profile of these CXCL8+ T cells, naïve and memory Tconv and Tregs were sorted, expanded, and analyzed by intracellular staining. As shown in Fig. 1F and Supporting Information Fig. 1A and B, on average 12.8%±1.6 of FOXP3+CD45RA+ Tregs and 19.8%±2.6 of FOXP3+CD45RA− Tregs expressed CXCL8. Neither

the CD45RA+CXCL8+ nor the CD45RA−CXCL8+ Treg populations co-expressed significant levels of IFN-γ or IL-17, further confirming that Ergoloid it is indeed the naturally occurring FOXP3+ Tregs that express CXCL8. A summary of CXCL8, IFN-γ, and IL-17 expression from expanded populations is seen in Supporting Information Table 2. To confirm whether FOXP3 directly regulates CXCL8 production, we investigated whether ectopic expression of FOXP3, which is known to reprogram Tconv cells into Tregs 16, modulates CXCL8 production. CD4+ T cells transduced with FOXP3 produced significantly more CXCL8 compared to control transduced cells, with the expected parallel suppression of IFN-γ production (Fig. 1G). Furthermore, FOXP3 directly transactivated the CXCL8 promoter, as evidenced by transient transfections using a CXCL8-promoter reporter construct (Fig. 1H). Together, these data conclusively demonstrate that FOXP3+ cells produce CXCL8 and indicate that FOXP3 directly regulates CXCL8 gene expression.

g. impaired viral clearance. Genetically modified DCs have also been employed in preclinical models of type 1 diabetes. BMDCs transduced with a lentiviral vector encoding IL-4 were able to prevent disease in old (12-week-old)

NOD recipients, i.e. well after the onset of insulitis, whereas unmodified DCs could not [60]. BMDCs engineered to express galectin-1 by transduction with a recombinant adenovirus were capable of delaying the onset of diabetes induced in immunodeficient NOD recipients by transfer of splenocytes from diabetic NOD females [61]. This is consistent with the recent finding that stimuli that induce tolerogenic DCs, such as IL-10 and 1,25-dihydroxyvitamin D3, also Y-27632 mouse increase their expression of galectin-1 [62]. In addition to viral vectors, treatment with anti-sense oligonucleotides has been used to engineer DCs having a tolerogenic phenotype. Giannoukakis and Trucco used anti-sense oligonucleotides targeting the CD40, CD80 and CD86 messages to treat BMDCs from NOD mice in order to Selleck Antiinfection Compound Library engineer phenotypically immature DCs [63]. When

these DCs were administered intraperitoneally to 5–8-week-old NOD mice, a single injection was able to prolong the time to diabetes onset. The therapeutic effect correlated with an increased percentage of splenic CD4+CD25+ (presumably regulatory) T cells. Systemic immunosuppression was not observed, as splenocytes from DC-treated mice were able to respond to alloantigens in vitro. These investigators showed subsequently that four weekly injections of anti-sense oligonucleotide-treated DCs, beginning at 8 weeks of age, resulted in prevention of disease in all recipients [50]. BMDCs from NOD mice have also been manipulated by treatment with decoy double-stranded oligonucleotides containing nuclear factor-kappa

B (NF-κB) binding sites [64]. The treated DCs exhibited reduced NF-κB activity and suppression of co-stimulatory molecule expression and IL-12 production. When administered as a single intravenous injection to NOD mice at 6–7 weeks of age, NF-κB-deficient DCs had a dramatic disease-preventive effect, while untreated DCs or those treated with control oligonucleotides were only modestly beneficial. When PtdIns(3,4)P2 contemplating therapeutic administration of DCs, it is important to consider the in vivo trafficking patterns of the administered cells. Creusot and Fathman showed that BMDCs administered intraperitoneally to mice accumulated preferentially in the pancreatic lymph nodes as opposed to other lymph nodes or the spleen [65]. This was the case even in non-diabetes-prone mouse strains. This could explain why intraperitoneal administration of anti-sense oligonucleotide-treated DCs delayed diabetes onset but did not result in systemic immunosuppression [63].

As one of the concerns, even in the face of culture-positive infections, is that commensal bacteria, such as coagulase negative staphylococci (CoNS), may indicate contamination from the skin flora, the presence of inflammatory cells at the site of localized microorganisms more strongly supports evidence of an infection. Criterion 6 also illustrates the difficulty of fulfilling Koch’s postulates for BAI. Koch’s postulates were designed to investigate the clinical consequences IBET762 of infection with a specific pathogen. Like many other complex infections with as yet poorly characterized

pathogenicity, BAI are not easily subjected to Koch’s postulates (Evans, 1976). BAI are often site-specific, associated with a medical implant or foreign body such as sutures, or have a host-specific component such as immune-suppression or predisposing risk (i.e. CF). More problematically, BAI may also be polymicrobial or associated with fastidious microorganisms that

are difficult to culture (Moter et al., 2010; Brook, 2011). As Evans (1976), and later, Fredricks & Relman (1996) point out, there are numerous infections where failing to fulfill Koch’s postulates did not eliminate the causative role Pirfenidone solubility dmso of a putative infectious agent in disease but only delayed it until adequate molecular, microscopic, or serological Nitroxoline evidence established the association of the causative agent in the disease. Indeed, in the case of cholera, Koch himself did not think that fulfillment of all postulates was sufficient (Evans, 1976; Fredricks & Relman, 1996). The failure to fulfill these postulates has frequently centered around two issues: the lack of appropriate culture methods for the putative infectious agent, and the technology available to demonstrate causation. The significance of previously unidentified microorganisms in a suspected biofilm infection provides additional

problems for clinical interpretation and can, in many cases, only be hypothesis generating, even though treatment attempts may have to be carried out. Supplementing Koch’s postulates in the context of a specific host response and suitable animal models specific for biofilm infections may be helpful (Jurcisek et al., 2005; Jurcisek & Bakaletz, 2007; Byrd et al., 2011). Modified Koch’s criteria have also been useful in CF where emerging pathogens also form biofilms (Høiby & Pressler, 2006; Hansen et al., 2010; Dalbøge et al., 2011). However, improved technology also offers several alternatives to culture, which are now used to detect and identify pathogens.