INVESTIGADORES
SALVA Maria Susana
capítulos de libros
Título:
Immunobiotics for the prevention of bacterial and viral respiratory infections
Autor/es:
VILLENA, JULIO; SALVA, SUSANA; BARBIERI, NATALIA; ALVAREZ, SUSANA
Libro:
Probiotics: Immunobiotics and immunogenics
Editorial:
CRC Press
Referencias:
Lugar: New Hampshire; Año: 2013; p. 128 - 168
Resumen:
In recent years enormous efforts have been made to unravel the
mechanisms of probiotic actions and various experimental approaches have
been developed to characterize the molecular basis of probiotic
effects. It has been shown that cell wall
components and DNA motifs from immunobiotic LAB can induce the
immunoactivation of GALT. Moreover, it was demonstrated that TLR2, TLR9,
NOD1 and NOD2 are able to recognize cell wall components and DNA of
dietary LAB, thereby contributing to immunoregulation in the GALT.
Although significant progress has been made in the knowledge of the
mechanisms of probiotics action in the gut, it is not known how some
immunobiotic strains are able to stimulate immunity in distal mucosal
sites from the gut when orally administered. Recent evidence showed that
pattern recognition receptors-mediated sensing of resident commensal
microbiota in the steady state regulates the development and function of
innate and adaptive immune systems in extra-intestinal sites, and
prepares the host to defend against intrusion by pathogenic
microorganisms. In mice, depletion of gut microbiota by antibiotics can
result in reduced surface expressions of TLR2 and TLR4 in peritoneal
macrophages, and less inflammation following intraperitoneal LPS
injection in vivo, indicating that intestinal microbiota can
constitutively prime peritoneal macrophages in preparation for pathogen
invasion. In addition, recognition of peptidoglycan from the microbiota
by NOD1 primes systemic innate immunity
by enhancing the cytotoxicity of bone marrow-derived neutrophils in
response to systemic infection with the bacterial pathogens, S.
pneumoniae and Staphylococcus aureus. Moreover, recent studies
characterized the cellular and molecular mechanism by which the gut
microbiota regulate respiratory tract immune defense against influenza
virus infections. Authors showed that commensal microbiota composition
critically regulates the generation of virus-specific CD4+ and CD8+ T
cells and antibody responses following respiratory influenza virus
infection. These authors speculated that a select group of commensal
bacteria, mainly neomycin sensitive bacteria (Lactobacilli) could
trigger TLRs to stimulate leukocytes either locally or systemically.
Then, the factors released by such leukocytes could support steady-state
activation of inflammasome-dependent cytokine release by respiratory
tract DCs improving their migration to the draining lymph nodes when a
viral infection occurs. Collectively, these studies indicate that the
gut microbiota support systemic and respiratory immunity by releasing
low levels of PRR ligands in circulation. Although our studies do not
allow us to discard this mechanism for the strains studied in our
laboratory (L. rhamnosus CRL1505 and L. casei CRL431), we propose a
different mechanism influencing antibacterial and antiviral immune
responses in the respiratory tract. Our results showed that there would
be a mobilization of cells from intestine (CD3+CD4+IFN-γ+ T and IgA+
cells) and changes in cytokine profile (IFN-γ and IL-10) that would be
able to beneficially modulate the respiratory mucosal immunity.
Activation of respiratory immunity by orally administered probiotics
would have a complex mechanism, probably related to specific strains.
Our studies also suggest that heat-killed LAB are also effective in the
immunomodulation of the systemic and respiratory immune system.
Therefore, probiotic bacteria in the form of live cells may not be
required for this purpose. The effect of non-viable L. casei and other
LAB on the respiratory immune system should be examined with more
detailed studies, as dead bacteria or their cellular fractions could be
an interesting alternative as mucosal adjuvants, especially in
immunocompromised hosts in which the use of live bacteria might be
dangerous. In addition, heat killed LAB have the advantage of allowing
longer product shelf-life as well as easier storage and transportation.
Further studies using immunomodulatory LAB strains able to stimulate
respiratory immunity as well as their cell components such as non-viable
bacterial particles, intact cell walls, cell wall
polysaccharide-peptidoglycan complex and chromosomal DNA are necessary
to find immunobiotic effector molecules (immunogenics) able to stimulate
immunity in distant mucosal sites from the gut.