There exist a substantial number of tests and technologies that enable tularemia-specific antibody monitoring, and that can be utilized in natural environmental studies [63]. == 3. of acquired humoral immune responses initiated byFrancisellainfection and their relationships with the immune defense systems, we take as our point of departure the June 2007 review article on this subject published by Elkins et al. Those authors exhaustively summarized the current state of knowledge at that time regarding the relationships betweenFrancisellamicroorganisms and the host immune system as obtained from animal models and the study of human infections up to their convalescence [1]. Dozens of reviews covering various VGX-1027 themes of induction, regulation, and expression of the hosts immune responses toFrancisellaat molecular and cellular levels have been published since that time. Thus, we have today general knowledge regarding innate immune recognition [2,3,4,5,6] and VGX-1027 the engagement of neutrophils [7,8,9], macrophages [10,11,12,13], and dendritic cells [14,15,16,17] during the phase of immune response expression. We nevertheless continue to have substantial gaps in understanding the processes duringFrancisellahost immune system interaction, wherein B cells and antibodies [18,19,20,21] might play significant roles during innate immune response, just as in the adaptive phase of immune response toFrancisellamicrobes. Important characteristics ofFrancisellaspecies include their abilities to infect a broad range of organisms, ranging from amoebas [22], ticks [23], mosquitoes [24], fish [25], amphibians [26], and birds [27,28] to diverse mammals, including rodents, lagomorphs, carnivores [29], monkeys [30], and humans NAV2 [31], and to accomplish their replication cycle in a diverse assortment of eukaryotic cells. TheFrancisellavirulence factors, the intracellular lifestyle ofFrancisella, and its interaction with individual cell organelles are not yet sufficiently understood. Similarly, difficulties in characterizing the molecular and cellular defense responses of an infected organism againstFrancisellaare due to the characteristic behavior ofFrancisella, which weakly activates cells of the mammalian innate immune system and actively suppresses host cell responses [32]. In particular, consequences of the relationships amongFrancisella, B cells, and natural and actively induced antibodies are still debated. Here, we summarize recent knowledge on this issue and present our view as to the role of antibodies during the interaction ofFrancisellawith the hosts cellular and molecular system of defense. The data regarding the antibodies againstFrancisellaoriginated from ecological and epidemiological studies, clinical data, experimental studies oriented upon theFrancisellahost immune system interactions, and studies devoted to the development of tularemia vaccines. == 2. Interactions of Hosts withFrancisellain Nature Leave Significant Antibody Traces == Because tularemia is widespread throughout the northern hemisphere, most studies came from Europe, Asia, and North America. Substantial numbers of wild and domestic animals, as well as humans, living in endemic foci of tularemia have serum antibodies againstF. tularensis. Seroprevalence of tularemia ranges from a few tenths of a percent to tens of percentage points, depending upon the area and season of screening. European wild small mammals (Apodemus flavicollis,Myodes glareolus,Sorex araneus,Apodemus sylvaticus,Apodemus agrarius,Microtus arvalis, and oneTalpa europaea) trapped at three localities in the Czech Republic were found to have antibodies againstF. tularensis, and the prevalence of antibodies was significantly different among animal species and sex [33]. Thirty-four blood samples from 656 Swedish wild predators and scavengers, among them brown bear (Ursus arctos), Eurasian lynx (Lynx lynx), raccoon dog (Nyctereutes procyonoides), red fox (Vulpes vulpes), wild boar (Sus scrofa), wolf (Canis lupus), and wolverine (Gulo gulo), had antibodies againstF. tularensissubsp.holarctica[34]. Substantial numbers of wild foxes (V. vulpes), raccoon dogs (N. procyonoides), and wild boars (S. scrofa) collected in several areas of Germany, as well as hunting dogs, were positive for antibodies toF. tularensis[35,36,37]. Exposure to wild and domestic animals expressing antibodies toF. tularensiswere identified as a risk factor for humans in European parts of Turkey [38,39]. Rodents studied in western Iran (Hamadan Province) and belonging to species of the Persian jird (Meriones persicus) and Libyan jird (Meriones libycus) were tularemia-seropositive and showed no cross-reactivity with brucellosis [40]. Some Japanese wild animals, including black bears, were shown to be seropositive toF. tularensisantibodies [41,42]. Seroprevalence to tularemia of wild animals has also been demonstrated in various parts of Russia [43,44,45], Armenia [46], and North America. Antibodies toFrancisellahave been detected in hares in Ontario, Alberta, and Nova Scotia [47,48,49,50], snowshoe hares, muskrats, and coyotes (Canis latrans) in Qubec [51], domestic VGX-1027 VGX-1027 dogs in New Mexico [52], prairie dogs in Texas [53], wildlife and humans in Alaska [54], and ground squirrels (Spermophilus beecheyi) in Oregon [55]..