Tips from the journals of the American Society for Microbiology

November 16, 2011

Annual Childhood Flu Vaccines May Interfere With Development of Crossresistance

Vaccinating children annually against influenza virus interferes with their development of cross-reactive killer T cells to flu viruses generally, according to a paper in the November Journal of Virology.

In this study, first author Rogier Bodewes of Erasmus Medical Center, Rotterdam, The Netherlands and his collaborators collected blood samples from Dutch children with cystic fibrosis, who are vaccinated annually against influenza, and from healthy control children who are not vaccinated, and tested both sets of blood samples for the presence of virus-specific killer T cells. The majority of virus-specific killer T cells are directed to conserved viral proteins, that is, proteins that are very similar among different flu viruses, unlike the rapidly evolving, highly variable proteins which are targets of antibodies induced by influenza vaccines.

In unvaccinated children, the investigators found that the number of virus-specific T cells rises with age, while such an increase was absent in children vaccinated annually. In fact, vaccination appeared to interfere with induction of such killer T cells, says Bodewes.

"Vaccinated children with [cystic fibrosis] will develop lower cross-reactive virus-specific CD8+ T cell responses than unvaccinated children," says the study.

"Most countries recommend annual flu vaccination of certain high risk groups to protect against seasonal influenza," says Bodewes. "Furthermore, some countries recommend annual influenza vaccination of all healthy children more than six months of age."

The research points up potentially conflicting policy outcomes. Annual flu vaccines are effective against seasonal flu, but could leave people more vulnerable to novel pandemics, says Bodewes, as induction of virus-specific killer T cells caused by childhood flu infection may reduce morbidity and mortality rates from pandemic influenza viruses. Referring to the paper, he says that the findings "highlight the need for the development and use of universal influenza A virus vaccines for children, especially in light of the pandemic threat of avian influenza A/H5N1." Nonetheless, he says that efforts to develop such vaccines have for several decades been stymied by the sheer complexity of targeting inner proteins.

(R. Bodewes, P.L.A. Fraaij, M.M. Geelhoed-Mieras, C.A. van Baalen, H.A.W.M. Tiddens, A.M.C. van Rossum, F.R. van der Klis, R.A.M. Fouchier, A.D.M.E. Osterhaus, and G.F. Rimmelzwaan, 2011. Annual vaccination against influenza virus hampers development of virus-specific CD8+ T cell immunity in children. J. Virol. 85:11995-12000.)






External Capsule Protects Gum Disease-Causing Bacteria From Immune Response

The capsule of Porphyromonas gingivalis, the bacterium that causes gum disease, provides stealth, boosting the bacterium's virulence, according to a paper published in the November Infection and Immunity. Call it a sugar coating, if you will, for in fact, the capsule is made from sugar molecules, which do not ordinarily elicit immunity. Thus it hides the bacterium's proteins within, preventing immune response.

In the study, the researchers, led by Janina P. Lewis of Virginia Commonwealth University, Richmond, compared the ability of normal, and mutant bacteria that were missing the capsule, to activate the immune system, to enter eukaryotic cells (the kind that are present in multicellular organisms), to cause disease, and to survive in mice. "The mutant bacteria activated the host to a greater extent, and thus, were more easily killed by eukaryotic cells," says Lewis. "Thus, the capsule protects the bacteria and allows them to survive unnoticed in our bodies."

Capsules also protect both bacteria and fungi, including P. gingivalis, as per this report, from being engulfed by the immune system's phagocytes (phago=eat; cyto=cell) and from being identified by dendritic cells as dangerous, thus marking them for destruction by antibodies. Conversely, in the study, mutant, non-encapsulated P. gingivalis were rapidly engorged by immune cells, and killed.

"Thus, anything that would interfere with generation of capsule, such as drugs interfering with the action of enzymes involved in synthesis of the sugar coat, could be used in treatment of periodontal disease, and importantly, could have broader implications for prevention of more serious diseases," by other encapsulated bacteria, such as pneumonia, anthrax, meningitis, endocarditis, and gastroenteritis, says Lewis.

(A. Singh, T. Wyant, C. Anaya-Bergman, J. Aduse-Opoku, J. Brunner, M.L. Laine, M.A. Curtis, and J.P. Lewis, 2011. The capsule of Porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence. Infect. Immun. 79:4533-4542.)




Probiotics Appear to Mitigate Pancreatitis: Surprising Hypothetical Mechanism Warrants Further Investigation

A probiotic treatment appears to mitigate pancreatitis in an animal model, leading to a new hypothesis of how probiotics may act, according to a paper in the November Applied and Environmental Microbiology. The bacterial species most closely associated with improvement in health was discovered for the first time in the course of this research.

Severe acute pancreatitis is a critical illness that is characterized by intestinal barrier dysfunction. While it is usually self-limiting, in 20 to 30 percent of cases patients develop serious disease, including systemic inflammatory response syndrome, sepsis, and/or multiple organ dysfunction, which frequently cause death.

In this study, Jacoline Gerritsen of University Medical Center, Utrecht, the Netherlands, and her collaborators gave one group of rats probiotic on a daily basis, beginning five days before they induced acute pancreatitis, and continuing briefly afterwards, before they sacrificed the animals. Another set of rats received a placebo.

The major finding: in the small intestine, higher than normal numbers of the newly discovered bacterium, "commensal rat ileum bacterium" (CRIB) were correlated with reduced severity of acute pancreatitis in animals that had been fed probiotic. These animals had less infection of remote organs, less infection of dying and dead pancreatic tissues, and less severe immune response during acute pancreatitis, as demonstrated by lower plasma levels of proinflammatory cytokines. CRIB, a member of the genus Clostridium, is not a constituent of the probiotic (Ecologic 641), but rather a benign bacterium that normally inhabits the lower gut. "...these results suggest that effects of this multispecies probiotic mixture... are mediated by stimulation of a not previously described gut commensal bacterium... which protects the host from severe sepsis," according to the report.

"This research has provided new knowledge on the possible mechanisms behind probiotic action," says Gerritsen. "In addition, it shows that bacterial species inhabiting the small intestine might be very important for health. Up until now, medical researchers have neglected the small intestine, because it is very difficult to obtain such samples from humans." That needs to change, she says.

(J. Gerritsen, H.M. Timmerman, S. Fuentes, L.P. van Minnen, H. Panneman, S.R. Konstantinov, F.M. Rombouts, H.G. Gooszen, L.M.A. Akkermans, H. Smidt, and G.T. Rijkers, 2011. Correlatin between protection against sepsis by probiotic therapy and stimulation of a novel bacterial phylotype. Appl. Environ. Microbiol. 77:7749-7756.)






Fleas Collected from Norway Rats in Downtown LA Carry Human Pathogen

Most fleas collected from rats trapped in downtown Los Angeles, California carried microbes from the genus, Bartonella, many of which are human pathogens, according to a paper in the November Applied and Environmental Microbiology.

The research team limited their investigation to fleas of the species Xenopsylla cheopis, because they are known both to infest Rattus norvegicus, the Norway rat, which is a major pest in high density urban areas, as well as to bite humans, says first author Sarah Billeter of the Centers for Disease Control and Prevention, Fort Collins, CO.

Bartonella species are gram-negative bacteria that infect red blood cells and endothelial cells of the host. More than half are thought to cause some clinical disease in humans. B. rochalimae, found in 72 percent of the collected fleas, was first isolated from the blood of a patient who became ill after returning to the United States from a vacation in Peru, says Billeter. "She complained of fever, insomnia, nausea, headache, and mild cough. Upon examination at the hospital, she was found to have recurrent fever, splenomegaly, and anemia." B. rochalimae has also been identified as a cause of infectious endocarditis in a dog from San Francisco, says Billeter.

The remaining fleas harbored sequences most closely related to B. tribocorum, a bacterium that has been detected in rodents "from various parts of the world," including France, says Billeter, and was isolated from the blood of a febrile Thai patient. "At this point, it remains unclear whether B. tribocorum is a human pathogen," says Billeter. "From a public health standpoint, however, it is important to determine whether R. norvegicus are reservoirs for zoonotic Bartonella spp. due to their close contact with humans and their pets." The question of whether X. cheopis can actually spread such pathogens to humans also warrants further investigation, says Billeter.

(S. A. Billeter,V. Gundi, M. P. Rood and M.Y. Kosoy, 2011. Molecular Detection and Identification of Bartonella Species in Xenopsylla cheopis Fleas (Siphonaptera: Pulicidae) Collected from Rattus norvegicus Rats in Los Angeles, California. Appl. Environ. Microbiol. 77:7850-7852)
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American Society for Microbiology

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