Activated macrophages with strong respiratory burst activity were also shown to be involved in the control of P. chabaudi infections in resistant C57BL/6 mice [109]. Although a number of studies have shown that IFN-γ is required for optimal macrophage activation [106], we recently showed that IFN-γ knockout mice could still control the acute phase selleck screening library of a nonlethal P. yoelii infection [107] and that this was

true in P. berghei NK65 infection (Couper KN, Greig R, de Souza JB & Riley EM, unpublished data). While most studies that suggest a role for IFN-γ in malaria have concerned P. chabaudi or P. falciparum, it is likely that its importance is parasite species specific. While reactive oxygen intermediates (such as superoxide and hydrogen peroxide) have been shown to be important in killing the parasites [110], this is a subject of debate; mice deficient in the NADPH oxidase system (gp91phox−/− mice or P47phox−/−) that are unable to make ROI are no more susceptible to malaria CH5424802 price infections than intact

mice [111], perhaps because of the presence of intrinsic ROI inhibitory mechanisms [112]. Experiments with NOS2− mice and with inhibitors of nitric oxide synthase discount a major role for nitric oxide in the killing of malaria parasites [111]. It seems that different parasite species may induce different macrophage responses, as P. yoelii parasites promote stronger respiratory bursts than P. berghei [113]. Human IFN-γ augmented the killing of P. falciparum parasites in vitro [114] through the activation of macrophages [115], and the parasites may also be killed by antibody-mediated phagocytosis through ADCI. Soluble plasmodial antigen bound to cytophilic IgG1 and IgG3 was as effective at stimulating monocyte killing via ADCI as the whole parasites [116]. Although a number of first- and second-generation vaccines have been clinically tested in the last 25 years, our knowledge of the correlates of protective

immunity still remains limited. Nevertheless, our original findings of killed PLEKHM2 whole blood-stage vaccines [21, 27] and recent data from trials of whole parasite vaccines suggest that T-cell activation, IFN-γ [21, 24-26, 29, 38, 43-45] and generation of cytophilic antibody subclasses–identified in our earlier publication [27] and later validated in human studies [81-83, 116]–are necessary for the establishment of protective immunity. Hence, our previous findings [21, 25-27] remain relevant to ongoing vaccine research [42-46], and importantly, they emphasize the value of mixtures of antigens combined with powerful adjuvants [25-27], not only to induce the necessary effector responses but to increase the possibility of inducing at least partial cross-strain immunity [10] by including a range of plasmodium epitopes.

[1] Dendritic cells are central to the generation of adaptive immunity, continuously sampling their vicinity for antigens against which the body might need to react, such as from invading pathogenic microbes. Antigens are taken up by DC in soluble or particulate forms, often facilitated by opsonization by antibody or complement, processed by a series of enzymes and then loaded onto MHC molecules for presentation to T-cells during priming of an immune response.[2]

MHC class II usually presents antigenic peptides derived from extracellular organisms to CD4+ T-cells, whereas MHC class I presents peptides derived from intracellular organisms (or cytoplasmic proteins) to CD8+ T-cells. This ensures that the optimum T-cell response is generated: CD4+ T helper cells for antibodies and cell-mediated immunity against extracellular organisms, and CD8+ cytotoxic T-cells against intracellular organisms and KU-60019 research buy cancers. The DC also receive inflammatory signals during infections and cancers; pathogen-associated molecular patterns or danger signals, which are recognized via receptors such as Toll-like receptors and stimulate cytokine secretion and co-stimulatory molecule expression, which further facilitates T-cell responses.

Hence, various vaccination strategies aim to target DC because of their pivotal role in adaptive immunity. Delivering antigens to DC, using strategies that target uptake via selleck products surface receptors, including DEC-205, mannose receptor and FcγR1, is an innovative area for developing vaccines and therapeutics. Heat-shock proteins (hsp) carry an antigenic profile or fingerprint of the cells from which they are derived, possess adjuvant activity and bind to receptors on DC to promote uptake. This review highlights the role of hsp in antigen delivery

to DC, which forms the basis of a strategy for developing vaccines against cancer and infectious diseases. Within cells, hsp undertake critical and conserved physiological roles. They function as chaperones and co-chaperones binding intracellular polypeptide chains and misfolded proteins, preventing aggregation and supporting folding and transport.[3] Most hsp have at least two functional domains: a polypeptide-binding domain, and an ATPase domain controlling binding and release selleck screening library of polypeptide substrate. Heat-shock proteins are present in organisms as diverse as bacteria and man, protecting proteins from damage during normal physiological activity as well as stressful conditions.[4] As a consequence of their physiological functions, hsp transport multiple proteins as ‘cargo’. Cellular levels of hsp are high, for example in bacteria, hsp70 alone accounts for 1–2% of cellular proteins after heat induction.[5] In eukaryotic cells hsp levels are increased by stressful stimuli including heat, oxidative stress, starvation, hypoxia, irradiation, viral infection and cancerous transformation.

An EcoRV restriction followed by a religation of the vector resulted in the deletion of the aa 86–99. All mutations were

verified by sequencing. Cells were washed with PBS/0.5% BSA and lysed on ice for 30 min using TKM lysis buffer (50 mM Tris/Cl, pH 7.5, 1% NP40, 25 mM KCl, 5 mM MgCl2, 1 mM NaVO4, 5 mM NaF, 20 μg/mL each Leupeptin/Aprotenin). After removing of cell debris by 15 min centrifugation Dabrafenib cell line at 21 000×g, proteins were separated by electrophoresis in denaturating SDS acrylamide gels (SDS-PAGE) and transferred onto PVDF membranes. The membrane was then probed with specific antibodies. Bound antibodies were detected with peroxidase coupled secondary antibodies. Immunoprecipitation was essentially done as described 38. Briefly, postnuclear lysates from PBT

were incubated overnight at 4°C with calmodulin Sepharose 4B (GE Healthcare). The samples were then washed five times and the proteins were solubilized in SDS sample buffer. A sample of the initial lysate and immunoprecipitates were applied to SDS-PAGE and analyzed by Western. To quantify proliferation, T cells were loaded with 0.5 μM CFDA-SE (Invitrogen, Karlsruhe, Germany) according to the manufacturer’s instructions. These labeled T cells were mixed 1:2 with superantigen loaded APC that were irradiated with 30 Gy to inhibit their proliferation or they were stimulated by crosslinked antibodies as described 17. Proliferation was determined after 3 days using a LSRII (BD-Bioscience). To measure the calcium flux, T cells Torin 1 mw were loaded with 5 μM (30 min/37°C) of the ratiometric calcium probe indo-1 (AM ester form). Detection of the ratio between calcium bound indo-1 (395 nm) and free indo-1 (495 nm) was done using an LSRII (BD Bioscience). The stimulation was performed by preincubation of the cell with 1 μg/mL anti-CD3 antibodies (OKT-3) on ice. A crosslinking antibody (7.2 μg/mL goat anti-mouse,

Dianova) induced the calcium flux during online measurement. The statistical analysis was performed with GraphPad Prism version 4.00. Two groups were compared using t-test or paired t-test for matched observation. Multiple groups Carbohydrate were compared using ANOVA. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG SA 393/3-3). The authors thank Finola Kirstein for cDNA cloning. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“Rabies virus Nishigahara strain kills adult mice after intracerebral inoculation, whereas the derivative RC-HL strain does not.

As shown in Figure 6, the suppressive activity of Treg

cells in MLN from sirolimus-treated mice was obviously stronger in comparison with that of PBS-treated mice. The data in this study clearly indicate that the significant immunosuppressive capacities of sirolimus, an inhibitor of mTOR, in TNBS-induced colitis resulted from a prominent increase of the functional activity of CD4+ CD25+ MG-132 chemical structure Treg cells. The observed enhancement of the potency of Treg cells might additionally be the result of a differential down-regulation of pro-inflammatory signals of DC subsequently favouring the education of Treg cells. Furthermore, the beneficial effect of sirolimus was also involved in down-regulation of IL-17-producing T lymphocyte (Th17) response in the perpetuation of Selumetinib price intestinal inflammation. Recent compelling evidence demonstrated that Th17 cells play a crucial role in the induction of autoimmune diseases.[11, 34] On the contrary, Treg cells actively restrain the inflammatory response, suppress development of autoimmune diseases and dampen a wide spectrum of immune responses.[8, 9] The differentiation of naive Th cells into Th17 or Treg cells is mainly driven by cytokine milieu. For example, TGF-β is a critical differentiation factor for the generation of Treg cells[35] and also directs FoxP3 expression, which is a specific marker in Treg cells

and is responsible for the function of these cells.[36] On the other hand, TGF-β, acting together with IL-6, induces the differentiation of pathogenic Th17 cells from naive T cells.[37] In addition, Th cell differentiation is manipulated by distinct transcription factors. For example, STAT5 and FOXP3 direct Treg see more cell differentiation and induce the production of regulatory cytokines such as TGF-β and IL-10,[38] and signal transducer and activator of transcription 3 (STAT3) and RORγt dominate

Th17 cell formation and IL-17 production.[39] Furthermore, the critical role of Th cell-intrinsic mTOR signalling, which regulates the differentiation between effector and Treg cells, has been well characterized.[40] Inhibition of mTOR can modulate the expression of FoxP3, IL-17 and RORγt genes directly, which contribute to induction of FoxP3 and suppression of Th17 polarization.[41] By inhibiting the mTOR signalling, sirolimus has been reported to promote Treg cell differentiation, proliferation and distribution[42] and suppress the formation of Th17 cells.[43] However, in inflammatory responses such as IBD, the role of mTOR inhibition in regulating Th17 and Treg cell differentiation has not been explored thoroughly. Here, we found that in the progression of TNBS-induced colitis, treatment with sirolimus, the inhibitor of mTOR, led to a significant increase in the percentage of CD4+ CD25+ Foxp3+ T cells in MLN and spleen (data not shown).

Infection of GEC results in acceleration through the cell cycle and suppression of apoptosis [26]. Antiapoptotic pathways activated by P. gingivalis include those involving JAK-Stat and PI3K-Akt, which consequently suppress intrinsic mitochondrial-mediated cell death (Fig. 1) [16, 27]. In addition, ATP scavenging by a secreted nucleoside diphosphate kinase enzyme of P. gingivalis prevents apoptosis through the P2X7 receptor

[28]. Nucleoside diphosphate kinase also contributes to intracellular persistence of P. gingivalis by increasing levels of glutathione that protect against ROS [29]. Long-term cohabitation of P. gingivalis within GECs leads to an overall subtle and nuanced interkingdom interaction, which can affect innate immune status. For example, click here P. gingivalis induces the production of a variety of microRNAs in GECs: e.g. miR-105 that suppresses TLR2 production [30] and miR-203 that inhibits SOCS3 and SOCS6 production (Fig. 1) [31]. Additional strategies employed by P. gingivalis to manipulate GEC innate immune function are discussed below. While oral epithelial cells can harbor several LBH589 price species of oral bacteria simultaneously [32], it is within the close confines of the multispecies biofilm on tooth surfaces that interbacterial communication becomes most relevant. As a strict anaerobe, P. gingivalis relies on antecedent colonizers such as streptococci

and Fusobacterium nucleatum to reduce the oxygen tension and also provide metabolic support [33]. Coadhesion among these organisms

facilitates nutritional and signaling interactions [34, 35]. Porphyromonas gingivalis develops Flavopiridol (Alvocidib) into heterotypic communities with Streptococcus gordonii following multimodal adhesion that involves both the FimA and Mfa1 component fimbriae of P. gingivalis that interact with streptococcal GAPDH and SspA/B surface proteins, respectively (Fig. 2). Engagement of Mfa1 with SspA/B initiates a signal cascade within P. gingivalis. Increased expression of a protein tyrosine phosphatase (Ltp1) ultimately elevates the amount of the transcription factor CdhR, which suppresses production of Mfa1 and constrains further community development [33-36]. Moreover, tyrosine phosphorylation/dephosphorylation also regulates protease expression by P. gingivalis, thus influencing pathogenic potential [37]. The ability of S. gordonii to enhance P. gingivalis pathogenicity has also been established in vivo: oral co-infection of conventionally reared (specific pathogen-free) mice with both organisms induces more alveolar bone loss compared to infection with either species alone [38]. In the oral cavity, S. gordonii, hitherto considered as a commensal, would therefore be more accurately categorized as an accessory pathogen [34]. Not all interspecies interactions are synergistic, of course.

It is likely that the failure to observe disease during this time period was secondary to the persistence of some Treg cells that maintained Foxp3 expression. A similar absence of disease induction was seen in another study in which Foxp3+ T cells were transferred to RAG−/− recipients [31]. While 50% of the cells lost expression of Foxp3, the recipients did not develop BMN 673 IBD. However, when the Foxp3− cells were isolated and transferred to secondary RAG−/− mice, the recipients did develop tissue inflammation. Taken together, GITR activation on Treg cells can

have different outcomes depending on the experimental context ranging from expansion in normal mice to death in the IBD model. This dual action of GITR engagement on Treg cells is not unexpected, as similar to other members of the TNFRSF, GITR might activate more than see more one signaling pathway. Activation of the NF-κB pathway may result in Treg-cell expansion [32], while GITR

signaling via Siva may result in apoptosis [33]. It also remains possible that the rapid induction of Treg-cell proliferation in a highly proinflammatory environment may result in activation-induced cell death via FAS/FAS-L or TNF/TNFR. Taken together, the translation of studies of GITR function in the mouse model to the use of Fc-GITR-L or agonist mAbs in man should be undertaken with caution depending on the disease (autoimmunity versus tumor immunity) under study and

the immune status of the host. C57BL/6 mice were obtained from PAK6 the National Cancer Institute (Frederick, MD). Foxp3-GFP mice were obtained from Dr. V.J. Kuchroo (Harvard University, Boston, MA) and maintained by Taconic Farms (Germantown, NY) under contract by NIAID. RAG−/− mice obtained from Taconic Farms. GITR+/− embryos (Sv129 × B6) were provided by C. Ricarrdi (Perugia University Medical School, Perugia, Italy). Rederived GITR+/− mice were backcrossed once with C57BL/6 mice, and the resulting progeny were screened for the mutant allele by PCR. The identified GITR+/− progeny were then intercrossed to generate GITR−/− mice. All mice were bred and housed at National Institutes of Health/National Institute of Allergy and Infectious Diseases facilities under specific pathogen-free conditions. All studies were approved by the Animal Care and Use Committee of the NIAID. Fc-GITR-L, construct #178–14, was prepared as previously described [15]. Anti-CD4 V-500 and PE-Cy5, anti-CD25 PE, anti-GITR-PE, anti-CD44 Alexa Fluor 700, CD45.2 allophycocyanin-eFluor 780, anti-CD45.1 PE-Cy7, fixable viability dye allophycocyanin-eFluor 780 and eFluor 450, anti-Foxp3 PE, eFlour 450 and allophycocyanin, ant-IL-17 Alexa Fluor 647 and anti-IFN-γ PE-Cy7 were purchased from (eBioscience, San Diego, CA).

In addition, Lee et al. have reported that VEGF is a potent stimulator of inflammation, airway remodeling, and

physiologic dysregulation that augments antigen sensitization and Th2 inflammation 17. In addition, PI3K/Akt check details signaling has been shown to increase levels of HIF-1α protein 18. However, there are little data on the roles and molecular basis of HIF-1α activation in allergic airway diseases. In the current study, we investigated the signaling networks involved in HIF-1α activation and the role of HIF-1α in pathogenesis of allergic airway disease using primary mouse tracheal epithelial cells and a murine model of OVA-induced allergic airway disease. The results showed that HIF-1α is activated in antigen-induced airway disease through PI3K-δ signaling. Activation of HIF-1α induces VEGF expression that is abnormally enhanced in asthma. Involvement of HIF-1α activation in VEGF expression in bronchial epithelial cells from OVA-treated mice was evaluated using siRNA for HIF-1α. The levels of nuclear HIF-1α protein and VEGF protein in primary tracheal epithelial cells

isolated from OVA-treated mice were increased compared with the levels in tracheal epithelial cells from the control mice (Fig. 1A). RNA interference using siRNA for HIF-1α reduced the increased levels of HIF-1α and VEGF in bronchial epithelial cells of OVA-treated mice. Additionally, RT-PCR and real-time RT-PCR analyses revealed that the increased mRNA levels of HIF-1α and VEGF were substantially decreased by the transfection of siRNA targeting HIF-1α (Fig. 1B–D). Western blot analysis 4-Aminobutyrate aminotransferase showed that levels CAL101 of nuclear HIF-2α protein and VEGF protein in primary tracheal epithelial cells isolated from OVA-treated mice were increased as compared with

the levels in tracheal epithelial cells from the control mice (Supporting Information Fig. 1A). The RNA interference with siRNA for HIF-2α reduced the increased levels of HIF-2α and VEGF in bronchial epithelial cells isolated from OVA-treated mice. Consistent with the results, RT-PCR and real-time RT-PCR analyses revealed that the increased mRNA levels of HIF-2α and VEGF were substantially decreased by the transfection of siRNA targeting HIF-2α (Supporting Information Fig. 1B–D). The effects of 2ME2, an inhibitor of HIF-1α translation, on HIF-1α protein levels were evaluated in nuclear protein extracts of lung tissues and primary tracheal epithelial cells isolated from OVA-treated and control mice. HIF-1α levels were increased in OVA-treated mice, as compared with the levels in the control mice (Fig. 2A, B, E, and F). The increased HIF-1α levels in nuclear protein extracts were decreased by in vitro treatment with 2ME2 (Fig. 2A and B) as well as by oral administration of 2ME2 (Fig. 2E and F). PI3K signaling has been shown to increase levels of HIF-1α protein 18.

Additionally, nephrin and CD2AP decreased and stained intermittently. Through the immunoelectron microscopy, different degrees of foot processes effacement were observed in the hypertensive group. Nephrin and CD2AP decreased and stained weakly along the podocyte basal membrane, while in the control group, they distributed evenly in podocytes. Conclusion: Hypertension induced dysregulation of podocyte cytoskeletal proteins, which may be an important cause that leads to the development of proteinuria and decline of renal function in hypertensive kidney injury patients. BOKUDA KANAKO1,2, MORIMOTO SATOSHI1, RYUZAKI

MASAKI1, MIZUGUCHI YUUKI1, OSHIMA YOICHI1, NIIYAMA MICHITA1, SEKI YASUFUMI1, YOSHIDA NAOHIRO1, WATANABE Pembrolizumab mw DAISUKE1, MORI FUMIKO1, ANDO TAKASHI1, ONO MASAMI1, ITOH HIROSHI2,

ICHIHARA ATSUHIRO1 1Department of Medicine II, Endocrinology and Hypertension, Tokyo Women’s Medical University, Tokyo, Japan; 2Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University, School of Medicine, Japan Introduction: The (pro)renin receptor[(P)RR] plays an important role in tissue angiotensin generation and in angiotensin-independent activation of intracellular signaling. Alisikiren, selleck chemical the direct renin inhibitor, effectively inhibits the first step of the renin-angiotensin system (RAS). In addition, it affects (P)RR-mediated actions and (P)RR expressions in experimental models. Aliskiren therefore may have organ protective effects, however, effects of single Aliskiren treatment on kidney and vascular functions still remain unclear. The soluble form of (P)RR [s(P)RR] is secreted into the extracellular space and serum level of s(P)RR is supposed to be a biomarker reflecting the status

of the tissue RAS. Herein, we examined the effects of Aliskiren on kidney and vascular functions and serum s(P)RR levels in hypertensive patients with chronic kidney disease (CKD). Methods: Thirty consecutive essential hypertensive patients with CKD in our outpatient clinic were randomly assigned to the Aliskiren (DRI) group or the Amlodipine, a calcium channel blocker, (CCB) group. Changes in parameters associated PAK5 with renal and vascular functions and indices of RAS components including serum s(P)RR levels were compared between the groups before and after 3- and 6-month treatment periods. Results: Office blood pressure (BP) was not significantly different between the groups before and after treatment. Plasma renin concentration and activity were significantly increased and decreased, respectively, in DRI group, while these remained unchanged in CCB group. There were no significant changes in serum s(P)RR levels throughout the treatment periods in both groups. Urinary albumin excretion was significantly decreased in DRI group, while no significant changes were observed in CCB group. eGFR remained unchanged in both groups.

brucei). The results obtained by analyzing DC surface

markers, Notch ligand mRNA, cytokines, asthma, and experimental autoimmune encephalomyelitis (EAE) models as well as performing microarrays indicate that both types of stimuli induce similar inflammatory, semi-mature DC profiles. DCs matured by TNF or VSG treatment expressed a common inflammatory signature of 24 genes correlating with their Th2-polarization capacity. However, the same 24 genes and 4498 additional genes were expressed by DCs treated with LPS that went on to induce Th1 cells. These findings support the concept of a default pathway for Th2-cell induction in DCs matured under suboptimal or inflammatory conditions, independent of the surface receptors and signaling pathways involved. Our data also indicate that quantitative differences in DC maturation might direct Th2- vs Th1-cell responses, since suboptimally matured inflammatory DCs induce default NU7441 molecular weight Th2-cell maturation, whereas fully mature DCs induce Th1-cell maturation. DCs play a fundamental role in the induction of adaptive immune responses as well as in the maintenance of peripheral tolerance 1–3. Through the expression of pattern-recognition receptors (PPRs)

such as Toll-like receptors (TLRs), DCs are able to sense a wide array L-gulonolactone oxidase of pathogens and mount an appropriate T-helper (Th) cell response 4. Naïve CD4+ T-cell precursors can differentiate into a variety of Th-cell lineages characterized by the cytokines produced: Th1 cells secrete predominately IFN-γ, Th2 cells release IL-4, IL-5, and IL-13 and Th17 cells typically produce IL-17 5. Although the contribution of DCs for CD4+ Th-cell polarization is under debate 6, several DC-derived mechanisms have been described to significantly direct Th-cell phenotypes. DCs change

their maturation status by upregulating surface expression of MHC class II and costimulatory molecules and by producing a defined set of cytokines to optimally induce distinct Th-cell responses 7–9. Due to their immunostimulatory function, DCs are of particular interest in immunotherapy settings, such as cancer therapy and infectious disease intervention 10, 11. Thus, the Th-cell polarizing profile defined by the maturation signature of DCs is of vital interest. Several membrane markers on DCs and soluble factors secreted by DCs have been described to polarize toward Th2 responses. These include costimulatory molecules such as OX40 12, ICOS-L 13, the Notch family member Jagged-2 14, the cytokine IL-6 15, or arachidonic acid metabolites such as PGE216–18. Much less is known about the factors that induce such Th2-instructing DC.

Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type β-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in non-tuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1κ), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous

mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-γ production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab Proteases inhibitor against sMTL-13, a response found to be

decreased following successful anti-tuberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin-like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment. Tuberculosis (TB) remains a major public health problem in both developing and industrialized countries 1, 2. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, is one of the most successful human pathogens and epidemiological studies estimated that one-third of the world population is infected with the bacterium 1, 2. Although Mtb remains viable in the majority of the infected subjects, only 5–10% of individuals develop active disease later in life 1, 2. However, the mechanisms for the breakdown of latency are largely unknown 3. Evidence suggests PLX3397 that both humoral and cellular immune responses are implicated in host resistance against Mtb and cell-mediated immunity is thought to be the major component for protection 1, 4–7. While effective immune responses are critical to control Mtb growth inside macrophages, it has been demonstrated that mycobacteria-associated factors play an important role in TB immunopathogenesis 8–10. Thus, secreted molecules are amongst

the possible candidates that influence pathogen–host interactions CHIR-99021 research buy in vivo. Secretion of proteins is a critical process for bacterial virulence. Mtb possesses a specialized secretion system to transport virulence factors across their unique cell envelope 11, 12. Although the study of culture filtrate protein (CFP) preparations from Mtb has revealed a myriad of proteins, there remain several other molecules annotated as having “unknown function” 13, 14. For example, Malen et al. using a proteomic approach, have recently detected 257 secreted proteins in CFP fractions from the laboratory strain Mtb H37Rv 13. However, no function has yet been ascribed to 23% of those molecules. Polypeptides secreted by mycobacteria may modulate inflammatory processes and could serve as targets for immune protection.