Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Abstract

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.

Antibody Response to Lyme Disease Spirochetes in the Context of VlsE-Mediated Immune Evasion

“…The affected lymph nodes remain persistently infected with B. burgdorferi spirochetes (54,55). Furthermore, germinal centers become structurally abnormal and fail to generate long-lived plasma and B cell memory cells for months (52). Thus, the present data indirectly support the idea that the LD pathogen requires only temporal suppression of the B cell response for fulfillment of its life cycle (52).…”

“…These changes may partially account for the reversed outcomes of superinfection for both VlsE-competent and -deficient B. burgdorferi clones between the two time points of infection. It is also possible that, at this early stage, the antibody response to non-VlsE antigens was transiently weakened via temporal suppression of germinal center (GC) B cell responses (52). As early as 24 h p.i., B. burgdorferi spirochetes tend to colonize murine lymph tissues, which results in destruction of T and B cell zones (53,54).…”

Suicide and Lyme and associated diseases

“…It is recognized Lyme disease Surveillance Case Definition based upon immune-based two-tier testing has a very low sensitivity (46%)105 and “generated over 500 times false-negative results than two stage HIV testing”. 106 The limitations of this testing are understandable since two-tier Lyme testing is an immune-based test for a highly adaptive spirochete that is well known to suppress and evade the immune system 12,107,108. This also explains the disparity between the number of CDC Surveillance Case Definition cases and the actual cases of Lyme disease each year 6,7.…”

Markers of innate and adaptive immunity in the skin and peripheral blood of patients with erythema migrans as an early manifestation of Lyme disease

“…При изуче-нии цитокинового профиля у больных МЭ в сыво-ротке крови исходно наблюдалось значительное по-вышение уровня провоспалительных цитокинов IL1b, IL-2 и IL-4, их средние значения составили (19,6±1,9 и 37,2±2,7 пг/мл) на фоне повышения 10,6±2,1 11 (10,4; 11,3) 9,3±1,6* 9,2 (9; 10,2) 11,2±2,4* 11 (11; 11,7) 2-я подгруппа (очаги более 30 дней) 6 5,8±1,6* # 5,4 (4,9) 6,8±2,5 6,6 (6,(2)(3)(4)(5)(6)(7)3) 4,2±1,5 3,9 (3,6) 8,3±1,7 8,3 (8,(1)(2)(3)(4)(5)(6)(7)(8)7) 16,4±2,5* 16,4 (15,(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)5) 21±4,6* 20,9 (18,(6)(7)(8)(9)(10)(11)…”

“…Получение статисти-чески достоверных данных об истинной заболевае-мости болезнью Лайма (ЛБ) затрудняется недоста-точностью пассивных обращений, а также ошибка-ми диагностики. Формирование хронического тече-ния инфекции, вызванной боррелиями, связано с количеством и биологическими свойствами возбу-дителя, уровнем резистентности и реактивности ма-кроорганизма [6,8,13,17,21]. В процессе размно-жения боррелии активно подавляют механизмы за-щиты хозяина, вызывая иммуносупрессию и спо-собствуя диссеминации возбудителя [9].…”