Lung B cells promote early pathogen dissemination and hasten death from inhalation anthrax.

Sampling of mucosal antigens regulates immune responses but may also promote dissemination of mucosal pathogens. Lung dendritic cells (LDCs) capture antigens and traffic them to lung-draining lymph nodes (LDLNs) dependent on the chemokine receptor CCR7 (chemokine (C-C motif) receptor 7). LDCs also capture lung pathogens such as Bacillus anthracis (BA). However, we show here that the initial traffic of BA spores from lungs to LDLNs is largely independent of LDCs and CCR7, occurring instead in association with B cells. BA spores rapidly bound B cells in lungs and cultured mouse and human B cells. Binding was independent of the B-cell receptor (BCR). B cells instilled in the lungs trafficked to LDLNs and BA spore traffic to LDLNs was impaired by B-cell deficiency. Depletion of B cells also delayed death of mice receiving a lethal BA infection. These results suggest that mucosal B cells traffic BA, and possibly other antigens, from lungs to LDLNs.

Development of a competitive index assay to evaluate the virulence of Listeria monocytogenes actA mutants during primary and secondary infection of mice.

We developed a competitive index assay for murine listeriosis that tests the virulence of Listeria monocytogenes strains in different organs and at various times postinoculation. Studies presented here demonstrate the reproducibility of this assay during primary and secondary infection of inbred and outbred mice. We verified the validity of this assay by performing competitive index analysis of a well-characterized strain of L. monocytogenes lacking the actA gene. In addition, we found that while L. monocytogenes strains unable to recruit vasodilator-stimulated phosphoprotein (VASP) to their surface exhibit a 10-fold virulence attenuation in the livers of naive animals, they display a 50-fold survival defect in the liver during secondary listeriosis.

Requirements for bone marrow-derived antigen-presenting cells in priming cytotoxic T cell responses to intracellular pathogens.

Bone marrow (BM)-derived antigen-presenting cells (APCs) are potent stimulators of T cell immune responses. We investigated the requirements for antigen presentation by these cells in priming cytotoxic T lymphocyte (CTL) responses to intracellular bacterial and viral pathogens. [Parent-->F(1)] radiation BM chimeras were constructed using C57BL/6 donors and (C57BL/6 x BALB/c)F(1) recipients. Infection of chimeric mice with either Listeria monocytogenes or vaccinia virus expressing the nucleoprotein (NP) antigen from lymphocytic choriomeningitis virus (LCMV) primed H2-D(b)-restricted, but not H2-K(d)-restricted CTL responses, demonstrating the requirement for BM-derived APCs for successful priming of CTL responses to these pathogens. Surprisingly, this did not hold true for chimeric mice infected with LCMV itself. LCMV-infected animals developed strong CTL responses specific for both H2-D(b)- and H2-L(d)-restricted NP epitopes. These findings indicate that in vivo priming of CTL responses to LCMV is remarkably insensitive to deficiencies in antigen presentation by professional BM-derived APCs.

H2-M3 restricted presentation of a Listeria-derived leader peptide.

Protective immunity to infection by many intracellular pathogens requires recognition by cytotoxic T lymphocytes (CTLs) of antigens presented on major histocompatibility complex (MHC) class I molecules. To be presented for recognition by pathogen-specific CTLs, these antigens must gain access to the host cell class I processing pathway. In the case of intracellular bacterial pathogens, the majority of bacterial proteins are retained within the bacterial membrane and therefore remain inaccessible to the host cell for antigen processing. We have isolated a CTL clone from a C57BL/6 mouse infected with the intracellular gram-positive bacterium Listeria monocytogenes (LM) and have identified the source of the antigen. Using a genomic expression library, we determined that the clone recognizes an antigenic N-formyl peptide presented by the nonpolymorphic murine MHC class Ib molecule, H2-M3. Several lengths of this peptide were able to sensitize cells for lysis by this CTL clone. The source of this antigenic peptide is a 23-amino acid polypeptide encoded at the start of a polycistronic region. Analysis of mRNA secondary structure of this region suggests that this polypeptide may be a leader peptide encoded by a transcriptional attenuator.

CTL responses to H2-M3-restricted Listeria epitopes.

Cytotoxic T cells (CTL) play a critical role in the murine immune response to Listeria monocytogenes (Listeria). Bacterial antigens are presented to Listeria-specific CTL by products of both conventional, polymorphic MHC class Ia and non-polymorphic MHC class Ib alleles. The H2-M3 class Ib gene product, M3, preferentially presents formylmethionine-initiating (fMet) peptides derived from the N termini of bacterial and mitochondrial proteins. Thus, M3 signals the presence of bacterial invaders to CTL effectors. Listeria-encoded fMet peptide epitopes for H2-M3-restricted CTL have recently been identified. These and other identified fMet peptides are predominantly comprised of hydrophobic residues and appear to be cleaved from membrane-bound proteins. The subcellular location and membrane topology of such proteins may be significant factors in their selection as target antigens for H2-M3-restricted CTL. Such rules may prove useful for prediction of candidate fMet peptide epitopes from other bacterial proteins and species. Studies using synthetic fMet peptides to stimulate CTL ex vivo are also discussed. These latter studies indicate that Listeria infection boosts H2-M3-restricted CTL responses. However, in contrast to MHC class Ia-restricted CTL responses, fMet peptide-specific CTL are observed in a large proportion of cultures from non-immunized, conventionally housed (non-SPF) mice. The CTL activity in these latter cultures may reflect priming in vivo on cross-reactive antigens, or may indicate that requirements for priming of H2-M3-restricted CTL are less stringent than for class Ia-restricted responses.

Primary and secondary immune responses to Listeria monocytogenes.

Recent studies have revealed the complexity of cytokine and cellular interactions required for resistance to primary Listeria monocytogenes infection and have illustrated that resistance to secondary infection may occur through multiple pathways. Analyses of Listeria epitope generation and the specificity of protective CD8(+) T cells have suggested that future research should focus on secreted protein antigens in specific resistance to infection and have increased our understanding of Listeria antigens presented by MHC class l-b molecules.

Identification of an H2-M3-restricted Listeria epitope: implications for antigen presentation by M3.

Using expression cloning, we have identified an H2-M3-restricted epitope of the intracellular bacterial pathogen Listeria monocytogenes. Picomolar concentrations of an amino-terminal N-formylated hexapeptide, fMIGWII, targeted cells for lysis by CD8+ cytotoxic T cells, while the nonformylated peptide was approximately 100-fold less active. The sequence of the 185 aa protein source of this epitope predicts a transmembrane protein that retains its N terminus and assumes an N(out)-C(in) topology. This membrane orientation offers an explanation for the protection of the epitope from deformylases present in the bacterial cell and suggests an explanation for the ability of phagocytes to present H2-M3-restricted bacterial epitopes via a vacuolar TAP-independent mechanism.

Tratamento da infeccao urinaria com acido pipemidico - consideracoes sobre 50 casos. / Treatment of urinary infection with pipemidic acid. Considerations on 50 cases

O presente trabalho estudou 50 pacientes, 18 homens e 32 mulheres, portadores de infeccao urinaria, tratados com acido pipemidico em capsulas na dosagem de 400 mg "per os" cada 12 horas por 10 dias conforme normas estabelecidas no protocolo de pesquisa. Como resultado obteve-se um indice de 88% de bons resultados. De acordo com os resultados obtidos, concluiu-se que o acido pipemidico e um dos antibacterianos de largo espectro de primeira escolha no tratamento das infeccoes do trato urinario

Bilharziose vesical por Schistosoma haematobium. / Vesical bilharziasis by Schistosoma haematobium

Os autores apresentam um caso de bilharziose vesical por Schistosoma haematobium, e comentam a raridade desta doenca em nosso meio. A clinica, a patologia, a propedeutica e a terapeutica sao descritas, enfatizando a atencao que se deve ter no esclarecimento de uma hematuria terminal e intermitente, em pacientes procedentes de zona endemica de Schistosoma haematobium

Endometriose vesical. / Vesical endometriosis

Os A.A. apresentam um caso de endometriose vesical com sintomatologia sugestiva mas cujo diagnostico so foi firmado durante o ato cirurgico. Havia comprometimento da parede vesical posterior possivelmente consequente a manobra abortiva com perfuracao de parede uterina anterior e parede vesical posterior.Tecem tambem breves consideracoes sobre a endometriose, estudando sucintamente a sintomatologia, o quadro clinico, metodos diagnosticos e terapeuticos. Realcam a importancia da associacao endometriose esterilidade