Influenza viruses and immune response

Μ. Exindari, Κ. Tsepanis, G. Gioula, Α. Melidou, Ν. Malisiovas, Ε. Diza
Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki

Influenza is continuously strongly connected to public health and therefore scientific research targets
the responsible microorganisms as well as the relevant human immunity mechanisms. The
recent 2009 pandemic is used as a research model in order to study the characteristics of the immune
response to influenza viruses. Initially, TLR7 acts as an important intracellular protype-recognizing
receptor (PRP) for influenza viral ssRNA. Then the action of MyD88 protein and the
activation of transcription factors leads to interferon I production and viral replication inhibition.
The same final result is reached by the intracellular RLR receptors, mainly the RNA helicase, RIG-I.
The intracellular NLR receptors, co-reacting with ASC protein and caspase-1, form an inflammasome
which induces the maturation of prodrome pre-inflammative cytokines and thus protection
against viral infections. The glycosylation site accumulation in A(H1) haemagglutinin molecules,
as an adaptive evolutionary strategy of influenza viruses, leads to a more successful recognitionby
the innate immunity and reduces the humoral immune response while leaving the cellular one
(CD8) unaffected; this may result to exaggerating cytotoxic reaction and the resulting cytokine
storm. The lack of glycosylation increases pathogenicity inhibiting viral clearance by the innate
immunity. Thus both mechanisms may cause increased cellular apoptosis and severe illness. Furthermore,
experimental data report that infections by highly pathogenic A influenza viruses were
followed by dendritic (subtype tipDC) cells accumulation in the lungs inducing even more CD8
cell proliferation. Influenza viruses often express tropism towards the upper or lower respiratory
system and they are reproduced and disseminated faster in younger hosts. Experimental data propose
that the local formation of induced broncho-associated lymphoid tissue (iBALT) in less young
influenza patients results to a more organized immune response. Old age affects negatively all
levels of immune reaction resulting to reduced lung inflammation and milder clinical symptoms.
Therefore more severe influenza cases seem to appear more frequently in younger people lacking
previous medical conditions.
The former contact between host and influenza viruses along with any antigenic similarity among
these viruses produces cross-reacting humoral and cellular immunity which provides increasing
protection in proportion to the age progress. The 2009 influenza pandemic seems to have unexpectedly
caused severe illness to much younger individuals than usual, while immune response
has played a dominating role to the process of the virus-human interaction. Thus valuable information
has been collected to be used for the prevention and treatment of future influenza epidemics
and pandemics.

Dientamoeba fragilis: an overlooked enteric parasite

E. Vassalou1,2, C.M. Vassalos2, A. Vakali2, N. Vakalis2, E.-T. Piperaki1, G. Vrioni1, A. Tsakris1
1Department of Microbiology, Medical School, National and Kapodistrian University of Athens
2Parasitology Laboratory, National School of Public Health, Athens, Greece

Dientamoeba fragilis is a cosmopolitan, amoeba-like protozoan living in the human gut. In the
past, it had been reclassified many times. Nowadays, it is thought to be an unflagellated flagellate.
Infection with D. fragilis is a specified protozoal intestinal infection that is often overlooked. In developing
counties, D. fragilis infection incidence ranges from 20 to 30%. Infection rates have been
also remarkably high in developed countries in the temperate climate zone. In Greece, our results
indicated for the first time a D. fragilis infection rate of 0.7%. It has been speculated to be transmitted
by faecal-oral route or via a helminth carrier. Zoonotic transmission has also been considered.
Up to date, only fragile trophozoites had been seen in human faecal samples. Most recently,
it has been claimed that D. fragilis cyst stage was microscopically observed in human stained faecal
smears. Dientamoeba’s pathogenicity and virulence still remain unclear. Immunocompetent patients
infected with D. fragilis can be presented with diarrhoea or with irritable bowel syndromelike
symptoms; asymptomatic infections have also been reported. A reliable diagnosis of D. fragilis
infection can be offered by microscopically examining permanently stained faecal smears, in the
context of clinical manifestations. In specialised laboratories, Dientamoeba can be xenically cultivated.
We developed a new simple medium containing an agar slant and a liquid phase with 4:1
ratio of 20% peptone solution to Locke solution; the medium was then compared with two different
xenic culture media on a case of known D. fragilis infection. There was no difference in the
growth curve of D. fragilis among the three culture media; however, the protozoan seemed to be
maintained for long in our newly developed medium. Advanced molecular methods have been
also employed for diagnostic purposes. Still, metronidazole remains the drug of choice; other therapeutic
options include modern imidazoles and tetracycline. Yet the nature, pathogenesis, diagnostic
approaches and treatment of D. fragilis infection largely remain unknown; thus, there is a
need to further investigate this parasitic infection now beginning to emerge in Greece.

Endothelial antigens – targets of alloresponse in renal transplantation

M. Kafetzi1, G. Vrioni2, V. Kapsimali2, A. Iniotaki1, A. Tsakris1
1General Hospital of Athens “George Gennimatas”
2Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens,

The human endothelial antigens are the first targets for the humoral and/or cellular alloresponse
because the endothelium is the tissue situated between the graft and recipient’s blood. The first
barrier for successful organ transplantation is the A and B blood group antigens followed by the
classical Human Leucocytes Antigens (HLA). Moreover, endothelial cells express non-classical HLA,
like the HLA-E, non-HLA antigens, like MICA (MHC Class I related chain A), autoantigens like vimentin
and proteins characterized by their molecular weight, like the 97-110kDa protein. This review
focuses on the endothelial antigens that are associated with successful renal transplantation.

The evolution of the Greek Microbiology through a bibliometric study of the publications of Acta Microbiologica Hellenica (1956-2014): Part C (2000-2014)

C. Tsiamis1, G. Vrioni1, E. Vogiatzakis2, A. Tsakris1
1Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
2Department of Microbiology, General Chest Hospital “Sotiria”, Athens, Greece

The period 2000-2014, is mainly characterized by studies on hospital infections and antimicrobial
resistance, a major problem of Public Health in Greece. The articles mainly focused on Gram-positive cocci
and Gram-negative aerobic bacteria, with Staphylococcus aureus, Enterococcus spp,
beta-haemolytic streptococcus Group A, Pseudomonas aeruginosa, Escherichia coli, Κlebsiella pneumoniae,
Salmonella Enteritidis και Neisseria meningitidis being primarily identified. The favorite
subjects of Virology were the influenza viruses (H1N1, H5N1, H3N2), the disease of hepatitis (HAV,
HBV, HCV), cytomegalovirus (CMV) and Parvovirus B19. During this period, besides the classical
fungal representatives (Candida, Aspergillus), we notice the gradual introduction of other fungal
species of medical interest, such as Fusariumspp. and Mucor spp. According to our findings, during
the period 1956-2014, the journal follows the Greek Microbiology evolution, the scientific
timeliness and the major infectious diseases and Public Health problems of the country.