Trichomonas vaginalis is identified as greatest public sexually transmitted disease

infected organs mainly liver and lungs and to some extent other organs including spleen, kidneys, heart, brain and bones of the animal carcasses. Prevention of cystic hydatid disease primarily focusing on veterinary investigations for controlling the extent and the intensity of echinococcosis in the definitive host populations, which indirectly may lead to control the prevalence of hydatid disease in the intermediate host animals. Treatment of cystic hydatidosis in livestock is still under investigation but anti-helminthes drugs can be used. Regular treatment, taking high degree of precautions when handling pets or dealing with animal meat must be taken into consideration to minimize the level of infection and egg excretion as well as the vaccination of ruminant intermediate hosts, are all in evaluation.

Bacillus thuringiensis subsp. israelensis is the most important biological insecticide for the control of mosquito vectors of disease. This bacterium produces toxins during sporulation that cause larval death by lysis of cells in their midgut. The pBtoxis plasmid of B. thuringiensis subsp. israelensis encodes all the mosquitocidal toxins and a number of other coding sequences. The plasmid also carries potential germination genes organised in a single ger operon. Comparison of the germination responses of spores from strains with and without pBtoxis revealed that this plasmid could promote activation of the spores under alkaline conditions but not following heat treatment. Introduction of the ger operon on a recombinant plasmid to the plasmidless strain established this operon as the first with an identified role in alkaline activation.

Activation of innate immunity is regulated by a variety of signaling molecules within

the immune cells. The present thesis was aimed to improve our understanding

innate signaling mechanism and their possible use as bio-indicators of exposure and

disease. The first part of the thesis deals with the involvement of TOM1L1 (Target

of Myb1 like 1) in innate immune signaling and regulation of inflammatory cytokines

in immune cells (study I and II). The initial event of T-cells activation depend

on the recruitment of Src family kinases Fyn and Lck, leading to interleukine-2 (IL-

2) production in T cells. Understanding the regulatory aspects of IL-2 induction in

T-cells is of importance as IL-2 is a key regulator for T-cell proliferation and survival.

Interaction screening indicated the ability of TOM1L1 protein to interact with

Fyn, and Lck, that is important for IL-2 production in Jurkat T-cells. TOM1L1

silencing decreased the levels of CD3/CD28 dependent induction of IL-2 in Jurkat

T-cells, and LPS dependent induction of TNF-α in THP-1. Furthermore, overexpression

of TOM1L1 in Jurkat T-cells causes an increase of STAT3 expression. This

was accompanied by an increase in the levels of IL-1β dependent induction of IL-6

and TNF-α in THP-1 cells. These results indicate that TOM1L11 participate in

regulation of innate immune response. The second part of the thesis deals with

development of innate immune signaling responses used as a diagnosis tools for

disease and exposure (study III and IV). Inflammatory diseases are associated with

innate immune reactions. In response to inflammation, the immune cells release

inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-10, TNF-α and CXCL8. These

cytokines are regulated by stress related kinases include MAP kinase proteins such

as ERK1-2, JNK, and MAPK p38, through activation of transcription factors AP-1,

ATF-2, and NF-AT. In a clinical study, it was observed that activated MAPK p38

has a potential role in the regulation of IL-10 expression in intermittent claudication.

However, expression of IL-10 and MAPK p38 was opposed in stable angina

group. Therefore, targeting MAPK p38 in inflammatory disease such as cardiovascular

diseases, diabetes, and rheumatoid arthritis might be useful in development of

treatment strategies. Innate immune reactions can also be used to monitor stress

related inflammatory responses following environmental exposure of immune cells.

Inflammatory responses of exposure were studied by in vitro exposure to waters

from sewage treatment works and recipient waters. The analysis shows that exposure

to inland waters can result in activated immune responses and that these responses

are both site dependent and vary over time.

Keywords: Innate immunity, TOM1L1, inflammatory responses.

Differences in activation between spores from strains of Bacillus thuringiensis subsp. israelensis with and without the toxin-encoding plasmid pBtoxis are demonstrated. Following alkaline activation, the strain bearing pBtoxis shows a significantly greater germination rate. Expression of just three genes constituting a previously identified, putative ger operon from this plasmid is sufficient to produce the same phenotype and characterizes this operon as a genetic determinant of alkaline activation.