Thinking Outside the Box: Innate- and B Cell-Memory Responses as Novel Protective Mechanisms Against Tuberculosis.

Tuberculosis (TB) is currently the deadliest infectious disease worldwide. Failure to create a highly effective vaccine has limited the control of the TB epidemic. Historically, the vaccine field has relied on the paradigm that IFN-γ-mediated CD4+ T cell memory responses are the principal correlate of protection in TB. Nonetheless, the demonstration that other cellular subsets offer protective memory responses against Mycobacterium tuberculosis (Mtb) is emerging. Among these are memory-like features of macrophages, myeloid cell precursors, natural killer (NK) cells, and innate lymphoid cells (ILCs). Additionally, the dynamics of B cell memory responses have been recently characterized at different stages of the clinical spectrum of Mtb infection, suggesting a role for B cells in human TB. A better understanding of the immune mechanisms underlying such responses is crucial to better comprehend protective immunity in TB. Furthermore, targeting immune compartments other than CD4+ T cells in TB vaccine strategies may benefit a significant proportion of patients co-infected with Mtb and the human immunodeficiency virus (HIV). Here, we summarize the memory responses of innate immune cells and B cells against Mtb and propose them as novel correlates of protection that could be harnessed in future vaccine development programs.

Genetic diversity of HLA system in two populations from Nuevo León, Mexico: Monterrey and rural Nuevo León.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ±â€¯0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ±â€¯4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ±â€¯4.30% by ML; 8.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Nayarit, Mexico: Tepic and rural Nayarit.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 161 Mexicans from the state of Nayarit living in Tepic (N = 97) and rural communities (N = 64), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Nayarit include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nayarit are Native American (50.79 ±â€¯5.03% by ML; 42.24% of Native American haplotypes) and European (37.04 ±â€¯6.21% by ML; 35.72% of European haplotypes), while African genetic component is less apparent but relatively high (12.17 ±â€¯2.50% by ML; 13.36% of African haplotypes).

Genetic diversity of HLA system in two populations from Durango, Mexico: Durango city and rural Durango.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 479 Mexicans from the state of Durango living in Durango city (N = 153) and rural communities (N = 326), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Durango include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in Durango are European (54.34 ±â€¯1.68%) and Native American (45.66 ±â€¯2.24%), while African genetic component was virtually absent (0.00 ±â€¯2.03%). However, African haplotypes could be estimated at a proportion of 9.13%.

Genetic diversity of HLA system in four populations from Baja California, Mexico: Mexicali, La Paz, Tijuana and rural Baja California.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 250 Mexicans from the states of Baja California Norte and Baja California Sur living in Mexicali (N = 100), La Paz (N = 75), Tijuana (N = 25) and rural communities (N = 50) to obtain information regarding allelic and haplotypic frequencies. The most frequent haplotypes for the Baja California region include nine Native American and five European haplotypes. Admixture estimates revealed that the main genetic components are European (50.45 ±â€¯1.84% by ML; 42.03% of European haplotypes) and Native American (43.72 ±â€¯2.36% by ML; 40.24% of Native American haplotypes), while the African genetic component was less apparent (5.83 ±â€¯0.98% by ML; 9.36% of African haplotypes).

Genetic diversity of HLA system in two populations from Sinaloa, Mexico: Culiacán and rural Sinaloa.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 286 Mexicans from the state of Sinaloa living in Culiacán (N = 103) and rural communities (N = 183) to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes for the state of Sinaloa include ten Native American most probable ancestry and five European most probable ancestry haplotypes. The admixture estimates revealed that the main genetic components in the state of Sinaloa are European (62.39 ±â€¯3.47%) and Native American (37.61 ±â€¯2.85%), while the African genetic component was estimated as virtually absent (0.00 ±â€¯1.86%).

Genetic diversity of HLA system in three populations from Guanajuato, Mexico: Guanajuato City, León and rural Guanajuato.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 262 Mexicans from the state of Guanajuato living in the cities of Guanajuato (N = 78), León (N = 22) and rural communities (N = 162), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes found in the state of Guanajuato include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Guanajuato are Native American (50.64 ±â€¯2.11% by ML, 43.35% of Native American haplotypes) and European (44.14 ±â€¯1.14% by ML; 39.35% of European haplotypes), while African genetic component is less apparent (5.22 ±â€¯2.08% by ML; 8.36% of African haplotypes).

Genetic diversity of HLA system in three populations from Chihuahua, Mexico: Chihuahua City, Ciudad Juárez and rural Chihuahua.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 461 Mexicans from the state of Chihuahua living in Chihuahua city (N = 119), Ciudad Juárez (N = 106) and rural communities (N = 236), to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes found in the state of Chihuahua include seven Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in Chihuahua are European (52.12 ±â€¯0.88% by ML; 41.53% of European haplotypes) and Native American (39.51 ±â€¯2.17% by ML; 37.45% of Native American haplotypes), while African genetic component was less apparent (8.36 ±â€¯1.47% by ML; 11.70% of African haplotypes).

Genetic diversity of HLA system in a population from Guerrero, Mexico.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 144 Mexicans from the state of Guerrero to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in the state of Guerrero include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Guerrero are Native American (61.36 ±â€¯2.69% by ML; 54.17% of Native American haplotypes) and European (35.01 ±â€¯4.59% by ML; 32.29% of European haplotypes), and a relatively low African genetic component (3.63 ±â€¯2.38% by ML; 5.90% of African haplotypes).

Genetic diversity of HLA system in a population sample from Aguascalientes, Mexico.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 95 Mexicans from the state of Aguascalientes to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes in the state of Aguascalientes include four Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Aguascalientes are Native American (54.53 ±â€¯3.22% by ML; 44.21% of Native American haplotypes) and European (44.34 ±â€¯0.45% by ML; 40.53% of European haplotypes), and a relatively low African genetic component (1.13 ±â€¯2.33% by ML; 5.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Michoacán, Mexico: Morelia and rural Michoacán.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 498 Mexicans from the state of Michoacán living in the city of Morelia (N = 150) and rural communities (N = 348), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Michoacán include 12 Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Michoacán are Native American (48.79 ±â€¯1.44%) and European (43.10 ±â€¯0.86%), while African genetic component is less apparent (8.11 ±â€¯0.85%). Our findings add to the growing knowledge on the population genetics of Western Mexico and provide new HLA data on populations from Michoacán.

Genetic diversity of HLA system in six populations from Jalisco, Mexico: Guadalajara city, Tlajomulco, Tlaquepaque, Tonalá, Zapopan and rural Jalisco.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 2046 Mexicans from the state of Jalisco living in the city of Guadalajara (N = 1189), Tlajomulco (N = 30), Tlaquepaque (N = 39), Tonalá (N = 35), Zapopan (N = 168) and rural communities (N = 585), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes found in the state of Jalisco include nine Native American most probable ancestry and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Jalisco are European (48.45 ±â€¯1.18% by ML; 41.66% of European haplotypes) and Native American (44.02 ±â€¯1.24% by ML; 39.86% of Native American haplotypes), while African genetic component is less apparent (7.53 ±â€¯0.30% by ML; 9.62% of African haplotypes).

Genetic diversity of HLA system in three populations from Sonora, Mexico: Ciudad Obregón, Hermosillo and rural Sonora.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 439 Mexicans from the state of Sonora living in Ciudad Obregón (N = 143), Hermosillo (N = 99), and rural communities (N = 197) to obtain information regarding allelic and haplotypic frequencies. We find that the 13 most frequent haplotypes for the state of Sonora include nine Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Sonora are European (51.25 ±â€¯2.90% by ML; 37.70% of European haplotypes) and Native American (43.35 ±â€¯2.57% by ML; 39.64% of Native American haplotypes), while the African genetic component was less apparent (5.39 ±â€¯2.54% by ML; 11.04% of African haplotypes).

Genetic diversity of HLA system in two populations from Chiapas, Mexico: Tuxtla Gutiérrez and rural Chiapas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 173 Mexicans from the state of Chiapas living in the city of Tuxtla Gutiérrez (N = 52) and rural communities (N = 121), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in Chiapas include 12 Native American and one European haplotype. Admixture estimates revealed that the main genetic components in Chiapas are Native American (71.61 ±â€¯0.58% by ML; 53.16% of Native American haplotypes) and European (26.39 ±â€¯5.05% by ML; 25.86% of European haplotypes), and a less prominent African genetic component (2.00 ±â€¯5.20% by ML; 9.77% of African haplotypes).

Genetic diversity of HLA system in two populations from Tamaulipas, Mexico: Ciudad Victoria and rural Tamaulipas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 148 Mexicans from the state of Tamaulipas living in Ciudad Victoria (N = 23) and rural communities (N = 125), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Tamaulipas include ten Native American, three European and one African haplotypes. Admixture estimates revealed that the main genetic components in the state of Tamaulipas are Native American (54.69 ±â€¯0.93% by ML; 47.65% of Native American haplotypes) and European (34.66 ±â€¯5.62% by ML; 33.56% of European haplotypes), and a relatively high African genetic component (10.65 ±â€¯5.05% by ML; 12.42% of African haplotypes).

Genetic diversity of HLA system in two populations from Hidalgo, Mexico: Pachuca and rural Hidalgo.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 122 Mexicans from the state of Hidalgo living in the city of Pachuca (N = 41) and rural communities (N = 81), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in Hidalgo include eight Native American and one European haplotypes. Admixture estimates revealed that the main genetic components in Hidalgo are Native American (58.93 ±â€¯2.16% by ML; 54.51% of Native American haplotypes) and European (32.49 ±â€¯2.88% by ML; 28.69% of European haplotypes), and a relatively high African genetic component (8.58 ±â€¯0.93% by ML; 6.97% of African haplotypes).

Genetic diversity of HLA system in seven populations from Veracruz, Mexico: Veracruz city, Coatzacoalcos, Córdoba, Orizaba, Poza Rica, Xalapa and rural Veracruz.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1113 Mexicans from the state of Veracruz living in the cities of Coatzacoalcos (N = 55), Orizaba (N = 60), Córdoba (N = 56), Poza Rica (N = 45), Veracruz (N = 171), Xalapa (N = 187) and rural communities (N = 539) to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes include 12 Native American haplotypes. Admixture estimates revealed that the main genetic components are Native American (64.93 ±â€¯1.27% by ML; 55.10% of Native American haplotypes) and European (26.56 ±â€¯0.89% by ML; 28.38% of European haplotypes), and a relatively high African genetic component (8.52 ±â€¯1.82% by ML; 8.78% of African haplotypes).

Genetic diversity of HLA system in two populations from Campeche, Mexico: Campeche city and rural Campeche.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 81 Mexicans from the state of Campeche living in the city of Campeche (N = 34) and rural communities (N = 47), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Campeche include ten Native American, three European, one African and one Asian haplotype. Admixture estimates revealed that the main genetic components in the state of Campeche are Native American (65.56 ±â€¯0.96% by ML; 51.24% of Native American haplotypes), European (34.44 ±â€¯10.94% by ML; 30.25% of European haplotypes), and a virtually absent African genetic component (0.00 ±â€¯10.31% by ML; 9.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Oaxaca, Mexico: Oaxaca city and rural Oaxaca.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 636 Mexicans from the state of Oaxaca living in the city of Oaxaca (N = 151) and rural communities (N = 485), to obtain information regarding allelic and haplotypic frequencies. We found that the 13 most frequent haplotypes in Oaxaca are all of putative Native American origin. Admixture estimates revealed that the main genetic components in the state of Oaxaca are Native American (73.12 ±â€¯2.77% by ML; 61.52% of Native American haplotypes) and European (17.36 ±â€¯2.07% by ML; 20.69% of European haplotypes), and a relatively high African genetic component (9.52 ±â€¯0.88% by ML; 8.94% of African haplotypes).

Genetic diversity of HLA system in two populations from Puebla, Mexico: Puebla city and rural Puebla.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 2827 Mexicans from the state of Puebla living in the city of Puebla (N = 1994) and rural communities (N = 833), to obtain information regarding allelic and haplotypic frequencies. We found that the 16 most frequent haplotypes in Puebla are all of them Native American. Admixture estimates revealed that the main genetic components in the state of Puebla are Native American (72.21 ±â€¯1.25% by ML; 63.30% of Native American haplotypes) and European (21.05 ±â€¯1.92% by ML; 23.86% of European haplotypes), and a less prominent African genetic component (6.74 ±â€¯2.20% by ML; 6.20% of African haplotypes).